Part 2: Anticancer Activity Ntawm Ntuj Thiab Synthetic Chalcones

Nyem qhov link kom tau qhov 1:https://www.xjcistanche.com/news/part1-anticancer-activity-of-natural-and-synt-54977104.html

Yog xav paub ntxiv, hu rautina.xiang@wecistanche.com

3. Anticancer Activity

Chalkonederivatives ua rau ntau lub hom phiaj, xws li aromatase, ATP binding cassette subfamily G tus tswv cuab 2 (ABCG2), mob cancer mis tiv thaiv protein (BCRP), activated nuclear B cell loj hlob yam (NF-kB), vascular endothelial kev loj hlob yam (VEGF), thiab tyrosine kinase receptors (epidermal growth factor receptor (EGFR) thiab mesenchymal-epithelial transition factor (MET), qhia txog kev ua ub no tseem ceeb hauv vitro thiab hauv vivo hauv kev mob qog noj ntshav thiab kev kho mob-tiv taus [161,162]. Kev cuam tshuam ntawm tubulin thiab cuam tshuam ntawm cov tebchaw no nrog kev sib dhos ntawm microtubules, cov ntsiab lus tseem ceeb rau kev tswj cov duab thiab kev ua haujlwm ntawm cov hlwb hauv cov txheej txheem ntawm mitosis thiab cell replication.apoptosis. Lub xub ntiag ntawm trimethoxyphenyl residue nyob rau hauv chalcone molecules yog qhov zoo rau cov irreversible antimitotic kev ua ntawm cov tebchaw, uas muaj peev xwm cuam tshuam nrog cysteine ​​residues nyob rau hauv tubulin los ntawm ib tug Michael-hom ntxiv tshuaj tiv thaiv [163]. Tsis tas li ntawd, kev hloov ntawm trimethoxyphenyl residue hauv chalcones nrog quinoline lossis quinazoline yog qhov zoo rau kev ua haujlwm tiv thaiv tubulin. Cov heterocyclic chalcones tsim hydrogen daim ntawv cog lus nrog tus so ntawm Cys241 thiab ruaj khov rau colchicine khi qhov chaw (zoo ib yam li combretastatin A-4, Figure7) [164,165].

3.1. Ntuj Chalcones nrog Anticancer Properties 3.1.1.Licochalcones (AD)

Cov hauv paus hniav thiab rhizomes ntawm qee hom Glycyrrhiza yog siv hauv cov tshuaj ib txwm siv rau kev kho mob plab, mob hawb pob, thiab mob. Ntau tshaj 600 lub tebchaw los ntawm licorice tau raug cais tawm, cov khoom tseem ceeb ntawm cov tshuaj lom neeg yog saponins thiabflavonoids. Ntawm cov flavonoids, series ntawm retrochalcones, licochalcones A, B, C, D, E, thiab G, thiab schematize tau txheeb xyuas. Muaj ntau cov kev tshawb fawb txog kev lom neeg ntawm licorice active compounds, qhov tseem ceeb tshaj plawsanti-inflammatory, antimicrobial, antioxidant, antiulcer, cytoprotective, thiab cytotoxic zog [166,167].

3.1.2. Licochalcone A

Licochalkone A (LA, Tables S1, thiab S2, Compound 1) yog ib qho flavonoid cais tawm ntawm Glycyrrhiza urakensis, G.glabra, thiab G.inflata (Fabaceae). Nws muajantitumor, anti-inflammatory, antimicrobial, antiparasitic, anti-obesity, antioxidant, thiab antiosteoporotic zog,AnticancerCov txiaj ntsig ntawm LA tau tshwm sim rau ntau hom qog noj ntshav, suav nrog cov qog nqaij hlav hauv plab BCG-823, HepG2, OVCAR-3, thiab SK-OV-3 (cov qog nqaij hlav zes qe menyuam) MCF{{ 5}}, thiab A549 [168-171]. Cov kev tshawb fawb qhia tias LA induces apoptosis ntawm U87 glioma cells, nasopharyngeal cancer hlwb, epithelial zes qe menyuam carcinoma cells, thiab zais zis qog nqaij hlav. Chalkone kuj muaj peev xwm ua kom autophagy thiab thaiv lub voj voog ntawm tes hauv cov qog nqaij hlav cancer mis. Tsis tas li ntawd, nws induces apoptosis los ntawm suppressing tshwj xeeb protein 1 nyob rau hauv lub mis mob cancer [172]. LA muaj tsawg cytotoxicity ntawm embryonic ntsws fibroblast hlwb. Tsis tas li ntawd, nws muaj peev xwm inhibit qog loj hlob thiab attenuate cis-platinum-induced toxicity [173]. Mechanisms uas flavonoids ua raws li cov tshuaj tiv thaiv kab mob muaj xws li inhibition ntawm Akt kev ua los ntawm suppressing hexokinase-2-kho qog glycolysis nyob rau hauv gastric cancer, downregulation ntawm metalloproteinase 2 qhia thiab induction ntawm apoptosis nyob rau hauv lub qhov ncauj hlwb, muaj peev xwm ntawm miR{16} }p ua kom muaj kev ntxhov siab nyob rau hauv endoplasmic reticulum thiab induce apoptosis nyob rau hauv tib neeg lub ntsws hlwb, txo PI3K / Akt / mTor activation thiab txo autophagy nyob rau hauv lub mis mob cancer, thaiv-ing G2 / M theem ntawm cell voj voog, repressing cell invasion los ntawm MEK / ERKand ADAM9signaling txoj hauv kev hauv tib neeg glioma hlwb, thiab inducing caspase-dependent apoptosis hauv tib neeg lub siab hlwb [174]. Lwm lub tswv yim uas LA nthuav tawm cov nyhuv cytotoxic muaj zog yog ROS-induced apoptosis. Piv txwv li, chalcone induces oxidative kev nyuaj siab thiab, yog li ntawd, apoptosis ntawm T24 hlwb (cell kab muab tau los ntawm tib neeg urinary zais zis carcinoma) los ntawm mitochondrial-dependent txoj kev thiab los ntawm inducing oxidative dab nyob rau hauv endoplasmic reticulum [175]. Lwm txoj kev tshawb fawb txog cytotoxicity thiab genotoxicity ntawm LA yog tsim los ntawm Bortolotto li al. LA tau muab piv rau trans-chalcone (Tables S1 thiab S2, compound 2). Cytotoxicity ntawm natural chalcones (LA thiab trans-chalcone) ntawm MCF-7 thiab 3T3 (embryonic fibroblast cell kab) tau txiav txim siab ntawm 24 thiab 48 teev. Cov txiaj ntsig tau qhia tias muaj kev ua haujlwm cytotoxic tom qab 48 teev ntawm kev kho mob. Kev soj ntsuam cytotoxicity MTT(3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) kev soj ntsuam tau pom cov lus teb ntawm koob tshuaj ntawm MCF{ {45}} hlwb kho nrog trans-chalcone thiab LA. Rau cov tshuaj ntsuam xyuas, genotoxicity tau pom tias zoo dua ntawm MCF-7 hlwb piv nrog 3T3 hlwb. DNA distortion ua rau covtiv thaiv kab mobmus qhib kom thiaj li tshem tau cov hlwb puas. Txawm li cas los xij, kev ua kom lub cev tiv thaiv kab mob kom txo qis DNA cov hlwb ua rau muaj kev cuam tshuam ntev. Tsis tas li ntawd, cellular teb rau degraded DNA tuaj yeem raug kho los ntawm inducing txoj hauv kev apoptotic intrinsic. G1 theem yog ib lub xeev uas ua ntej DNA replication, nyob rau hauv uas tej yam xws li cellular tej yam kev mob (metabolism, signaling, thiab cell loj) cuam tshuam qhov kev loj hlob ntawm lub cell voj voog, ua rau DNA rov tsim nyob rau hauv hlwb los yog pib cov txheej txheem ntawm apoptosis.IC50 ntawm LA ua 60,46m. Trans-chalcone induces cell voj voog blockade nyob rau hauv G1 theem thiab intensifies cellular apoptosis. Nws tau raug pom zoo tias kev kho mob nrog LA thiab trans-chalcone induces apoptosis los ntawm txoj kev mitochondrial, xav tias induction ntawm cov noob tseem ceeb ntawm txoj kev no tshwm sim tom qab 24 teev, xws li protease activator factor 1 ntawm protein apoptosis thiab protein X txuam nrog Bcl {{ 9}} ib. Txawm hais tias MCF-7 cov kab ntawm tes paub tias muaj qhov tsis txaus caspase 3, txoj kev tshawb fawb pom tias kev kho mob nrog cov chalcones induces cleavage ntawm poly (ADP-ribose) polymerase (PARP), ib tug polymerase uas nws cleavage mus rau hauv ob seem yog ib qho qhia. ntawm apoptosis. Kev tsim txom

ntawm Bcl -2 gene los ntawm LA thiab trans-chalcone hauv kev sim PCR tsom xam pom, ntawm qib protein, kev tswj hwm koob tshuaj rau MCF-7 hlwb thiab kev sib haum xeeb hauv nruab nrab. Cyclin D1 yog lwm cov protein ua rau ntawm MCF-7 cov kab ntawm tes hauv qhov muaj chalcones. Cov protein no yog qhov tseem ceeb rau kev loj hlob ntawm G1 mus rau theem S thiab yog ib qho tseem ceeb biomarker rau qee cov qog nqaij hlav, nrog rau mob qog noj ntshav. Rau cov laj thawj no, cyclin D1 degradation yog lub hom phiaj txaus nyiam rau kev txheeb xyuas cov tshuaj tiv thaiv kab mob tshiab thiab cuam tshuam nrog kev cuam tshuam ntawm cell cycle [176].

Qui et al. kuj tau tshuaj xyuas cov txiaj ntsig ntawm LA ntawm lub ntsws qog nqaij hlav hauv vitro. Kev kho mob Flavonoid txo qis kev muaj peev xwm ntawm A549 thiab H460 hlwb (tib neeg uas tsis yog-me me ntawm lub ntsws carcinoma), qhov kev hloov pauv no tau cuam tshuam los ntawm koob. Tag nrho ntawm 40 μM ntawm lichohalcone inhibits kev loj hlob ntawm cov qog nqaij hlav ntsws los ntawm 45-80 feem pua. Tom qab 24 lossis 48 teev ntawm kev kho mob. Tsis tas li ntawd, qhov sib xyaw ua rau muaj cytotoxicity tsawg ntawm tib neeg lub ntsws epithelial hlwb, txhawm rau qhia seb puas yog ib qho ntawm cov txheej txheem ntawm inhibition ntawm lub ntsws cancer cell loj hlob los ntawm LA yog cell cycle blockade, cell kab tau kho nrog sib txawv. Cov ntsiab lus ntawm cov khoom sib xyaw rau 16h ces lub voj voog ntawm tes tau txheeb xyuas los ntawm kev khiav cytometry.Cov txiaj ntsig tau pom tias, nyob ntawm qhov koob tshuaj, chalcone blocks G2 / M theem ntawm A549 thiab H460 hlwb. /propidium iodide colorimetric method. Cov txiaj ntsig tau pom tias muaj kev sib sau ntawm cov hlwb apoptotic hauv LA-kho pab pawg, uas yog nyob ntawm cov concentration siv. Iated nrog apoptosis tau kuaj los ntawm Western blot txoj kev. Qib ntawm PARP thiab cleaved caspase 3 tau nce siab, thiab pre-caspase 3 antiapoptotic proteins, PARP, Bcl-xL, thiab Bcl-2 raug txo qis 20 teev tom qab kho chalcone. Cov txiaj ntsig no qhia tau tias LA-induced apoptosis yog txuam nrog PARP/Bcl{20}} txoj kev [177]. Cov qauv molecular pom tias LA tau docked hauv ATP khi hnab ris ntawm EGFR, suav nrog exon 19 deletion kev hloov pauv, L858R ib qho kev hloov pauv, L858R / T790M ob qhov kev hloov pauv, thiab hom tsiaj qus. Hauv L858R / 790M kev hloov pauv, LA muaj peev xwm cuam tshuam nrog Lys745 los ntawm kev sib cuam tshuam cation-II. Hydrogen bonds yog tsim los ntawm WT EGFRand licochalcone ntawm Met793, Lvs745, thiab Asp 855. Exon 19 deletion muaj peev xwm hloov cov duab ntawm lub hnab tshos uas muaj kev cuam tshuam nrog licochalcone raug suav tias tshwm sim, tsim hydrogen bonds nrog Met793, Thr7762, thiab Glu. . Cov ntaub ntawv tau txais los ntawm kev tshuaj xyuas silico ntawm LA yog qhov tseem ceeb rau kev txheeb xyuas cov tshiab, xaiv EGFR inhibitors ntawm ntau hom kev hloov pauv [178].

Nyem kom tau txais cov ntaub ntawv ntxiv. ntawm kev tiv thaiv

3.1.3. Licochalcone B

AnticancerCov teebmeem ntawm licochalcone B (LB, Tables S1, thiab S2, compound 3) tau pom los ntawm kev tshuaj xyuas ntawm cov kab sib txawv ntawm tes, suav nrog tib neeg lub hlwb los ntawm qog nqaij hlav qog noj ntshav T24 thiab EJ, qog nqaij hlav hauv qhov ncauj HN22 thiab HSC4, MCF-7, A375. (ib tug tib neeg melanoma cell kab), thiab A431 (squamous cell carcinoma). Cov kev tshawb fawb tau pom tias LB cuam tshuam kev loj hlob ntawm cov qog nqaij hlav cancer, inhibits kev tsim ntawm metastases, thaiv lub voj voog ntawm tes, thiab induces apoptosis [161]. Kang et al.investigated lub molecular mechanism uas LB induces apoptosis nyob rau hauv tib neeg melanoma thiab hlwb nyob rau hauv squamous cell carcinomas. Licochalcone tau pom tias ua rau apoptosis ntawm A375 thiab A431 hlwb los ntawm ob txoj hauv kev thiab sab hauv. Nyob rau hauv cov ntaub ntawv ntawm kev soj ntsuam cov nyhuv antiproliferative ntawm chalcone nrog trypan xiav staining, nws tau pom tias LB induces ib tug tseem ceeb txo nyob rau hauv cell viability, qhov no txo ​​yog correlated nrog con-centration Tom qab qhov sib ntxiv ntawm LB, cov kev hloov tseem ceeb ntawm cov yam ntxwv ntawm tes tau pom, suav nrog. cell contraction, rupture ntawm cell membranes, thiab nce nyob rau hauv feem pua ​​ntawm fragmented nucleus hlwb. Ntxiv feem pua ​​​​ntawm cov pre-G1-phase cells thiab apoptotic cells kuj tau sau tseg [38]. Lwm txoj kev tshawb fawb pom tias LB cuam tshuam lub voj voog ntawm tes hauv G2 / M theem nyob rau hauv rooj plaub ntawm HepG2- hom kab mob qog noj ntshav, thiab nyob rau hauv cov ntaub ntawv ntawm lub zais zis thiab lub mis qog hlwb, compound blocks S theem [179]. Nkauj et al.highlighted the suppressive effect of LB on the growth of JAK2-type esophageal carcinoma squamous cells. Cov kev tshawb fawb docking tau ua nrog Autodock Vina software, uas tau siv los kwv yees hom kev khi. Cov qauv ntawm JAK2 receptor nrog inhibitory muaj peev xwm muaj nyob hauv Protein Data Bank (PDB nkag 2B7A, residues 840-1.132). IAK2 ua lub luag haujlwm tseem ceeb, ua tus neeg nruab nrab hauv nruab nrab ntawm cytokine signaling, thiab yog tyrosine kinase protein ntawm JAK tsev neeg. ATP khi ruaj khov rau

magnesium ions hauv catalytic domain ntawm tyrosine kinases. Nyob rau hauv qhov chaw docking, qhov loj ntawm qhov chaw tshawb nrhiav suav nrog ATP qhov chaw sib txuas uas pom los ntawm cov seem 855-863 thiab 822, qhov twg ATP tau suav nrog ntau yam muaj peev xwm JAK2 inhibitors. Hauv kev twv ua ntej, LB ligand tau ua nrog Marvin Sketch software. Tom qab docking, qhov zoo tshaj plaws peb txoj kev sib khi sib txawv tau sau, uas muaj qhov sib xws. Cov lus xaus ntawm kev kwv yees tau pom zoo txog kev cuam tshuam ntawm LB nrog ATP khi hnab ris ntawm JAK2[180,181].

3.1.4.Licohalcone C

Licochalcone C (LC, Tables S1, thiab S2, compound 4) paub tias yuav txo tau cov kab mob ntawm cov kab mob monocyte. Qhov no yog vim qhov txo qis hauv iNOS kev qhia thiab kev rov ua haujlwm ntawm cov tshuaj tiv thaiv antioxidant network ntawm superoxide dismutase, catalase, thiab glutathione peroxidase. Kwak et al. tau ua txoj kev tshawb fawb los piav txog kev sib raug zoo ntawm ROS, c-Jun NH2 terminal kinase (INK), thiab p38mitogen-activated protein kinase (MAPK) thiab tsim qhov cuam tshuam ntawm LC hauv inducing apoptosis ntawm KYSE 30 thiab KYSE450 esophageal cancer cell kab. Cov kev tshawb fawb yav dhau los tau txiav txim siab IC50 qhov tseem ceeb rau kev kho mob LC (45 ug / mL) tom qab 24 teev los tiv thaiv kev loj hlob ntawm A549, MCF-7, thiab T24 cell kab. Inhibitions ntawm 40,47 thiab 68 feem pua ​​tau txais rau peb kab ntawm tes. Kwak et al. tau koob tshuaj- thiab lub sij hawm-nyob rau hauv vitro inhibition ntawm esophageal cancer cell proliferation. Los ntawm tsib lub xov tooj ntawm tes txheeb xyuas, KYSE30 thiab KYSE450, uas muaj kev txhawb nqa caj ces, muaj cov lus teb zoo sib xws rau kev kho LC. Hauv kev txheeb xyuas ntawm kev loj hlob ntawm kev ywj pheej ntawm kev ywj pheej hauv cov mos mos agar, cov txiaj ntsig qhia tau hais tias qhov txo qis hauv lub peev xwm ntawm KYSE30 thiab KYSE450 hlwb los tsim cov cheeb tsam. Nyob ntawm seb qhov concentration, chalcones induced apoptosis nyob rau hauv ob lub cell kab. Qhov sib xyaw ua ke kuj ua rau muaj kev tswj hwm nce siab ntawm p24 thiab p27 (tsis zoo hloov pauv cov tswj hwm hauv G1 thiab S theem ntawm lub voj voog ntawm tes) thiab tswj kev downstream cyclin D. LC kuj nce ROS tiam hauv KYSE30 thiab KYSE450 hlwb. ROS qhib txoj kev mitogen-activated protein kinase (MAPK) thiab inducecell apoptosis. Tsis tas li ntawd, qhov sib xyaw ua ke tau nce qib ntawm JNK, c-Jun, thiab p38 phosphorylation thiab qhib txoj hauv kev apoptotic [182]. Zoo ib yam li kev kawm docking los ntawm Song et al. rau LB[180], Oh et al.highlighted binding kev sib cuam tshuam ntawm LC thiab tib neeg JAK2 hlwb. Docking simulation tau ua tiav siv Autodock Vina. Txhawm rau pib txoj kev kawm docking, tus qauv ntawm JAK2 receptor, uas tau daws los ntawm kev sim X-ray, tau txais los ntawm Protein Data Bank (PDB nkag 2B7A). Cov qauv ntawm LC ligand yog qauv los ntawm Marvin Sketch software thiab optimized los ntawm Chimera software. Qhov chaw catalytic ntawm JAK2 tau txheeb nrog thaj tsam pob khawm (cov seem 929-935), DFGloop (residues 994-996), thiab Ploop (residues 858-865). Lub voj-zoo li lub pob khawm yog qhov tseem ceeb rau kev paub txog ATP thiab tsim cov ntawv cog lus hydrogen nrog cov khoom. DFGloop muaj peb cov amino acids (aspartic acid, phenylalanine, thiab glycine) thiab cuam tshuam nrog kev khi ntawm cov hlau uas xav tau rau catalytic phosphorylation. Ploop muaj txiaj ntsig zoo rau kev ruaj khov thiab tsim kev sib cuam tshuam nrog ligands. Raws li tuaj yeem pom, qhov kev twv ua ntej ntawm kev sib khi ua tau tau ua nyob rau hauv peb qhov chaw ua haujlwm. Docking txoj kev tshawb fawb pom tias LC cuam tshuam nrog ATP khi qhov chaw rau JAK2 thiab qhia tias JAK2 yog lub hom phiaj ncaj qha ntawm nws. Chalcone tseem txwv tsis pub JAK2 autophosphorylation los ntawm kev khi rau ATP hnab ris ntawm p-JAK2 [183,184].

3.1.5. Licochalcone D

Licochalcone D (LD, Tables S1, thiab S2, compound 5) yog ib qho active flavonoid cais los ntawm Glycyrrhiza inflata. Ib txoj kev tshawb fawb tau ua los ntsuas lub peev xwm ntawm LD los tiv thaiv kev loj hlob ntawm tes los ntawm ob lub hom phiaj rau cov qog nqaij hlav ntsws (EGFR thiab MET) siv cov hlwb rhiab heev thiab gefitinib-resistant tib neeg. Txhawm rau nkag siab txog kev sib txuas ncaj qha ntawm chalcone rau EGFR thiab MET, gefitinib-sensitive cell kab (HCC827) thiab gefitinib-resistant cell kab (HCC827GR) tau siv. Cov txiaj ntsig ntawm kev ntsuam xyuas qhia tau hais tias flavonoid khi rau ob receptors, inhibiting kev ua ntawm EGFR thiab MET kinases raws li kev sib tw inhibitor ntawm ATP. Hauv EGFR complex, chalcone muaj ob daim ntawv cog lus hydrogen tsim los ntawm Met793 ua lub ntsiab lus tseem ceeb thiab lub kaum sab xis ntawm Asp855 hauv DFG voj.4-Hydroxy-3-(3-methyl tab sis{{13} }enyl)phenyl pawg thiab 3,4-dihydroxy-2- pawg methoxyphenyl raug kho rau tib lub dav hlau thiab thaiv ntawm hydrophobic residues Leu718, Val726, thiab Ala743 ntawm P loop thiab Leu 844. Hauv Met complex, kev keto

pab pawg ntawm chalcone tsim ib daim ntawv cog lus hydrogen nrog Met1160. Tyr1159 ua lub ntsiab lus tseem ceeb thiab le1084, Vall092, Ala1108, thiab Lys1110 ntawm Ploop tau them zoo ib yam nrog lub hau. Luis tseem muaj kev txhawb nqa los ntawm sab hydrophobic chains ntawm Met1160 lub ntsiab lus tseem ceeb thiab Leu1140, Met1211, thiab Ala1221 ntawm qis ATP hnab tshos.EGFR khi txoj hauj lwm zoo li MET binding txoj hauj lwm, tsim hydrogen bonds thiab hydrophobic kev sib cuam tshuam. Chalkone yog nyob rau tib yam hauv cheeb tsam khi rau ob lub receptors. Stabilization ntawm complex tuaj yeem nce los ntawm kev sib cuam tshuam hydrophobic. Cov txiaj ntsig tau kwv yees tau muab piv nrog cov ntaub ntawv sim, qhia tias flavonoid sib tw inhibits ob receptors [185].

3.1.6. Xanthohumol

Prenyl chalcones, vim lawv cov qauv sib txawv, muaj cov khoom siv lom neeg sib txawv, suav nrog kev tiv thaiv kab mob, tshuaj tiv thaiv kab mob, thiab kev ua haujlwm antimutagenic [186]. Cov kev tshawb fawb tau pom tias ntuj chalcones nrog cov pab pawg prenyl muaj peev xwm cuam tshuam nrog p53. Piv txwv li, kev kho ntawm A549 hlwb nrog prenyl chalcone xanthohumol (XN, Tables S1, thiab S2, compound 6) induces apoptotic cell tuag thiab blocks cell voj voog nyob rau theem G1. Cov kev ua ub no yog vim muaj kev tswj hwm ntawm p53 thiab p21 los ntawm lub voj voog ntawm tes thiab kev txo qis ntawm cyclin D1. Apoptosis yog tshwm sim los ntawm kev ua haujlwm ntawm caspase 3 [187].

XN((3'-(3,3-dimethylallyl)-2',A',4-trihydroxy-6'methoxychalcone) yog cov feem ntau prenylated flavonoid ({{7 }} 1-1 feem pua ​​​​ntawm qhov hnyav qhuav) ntawm poj niam hop inflorescences (Humulus lupulus)[180]. XN kuj yog ib qho ntawm cov npias, ib qho kev noj haus loj ntawm prenylatedflavonoids, qhov twg nws muaj nyob rau hauv cov concentrations saum toj no 0.96 mg/L.Vim nws cov kev ua ub no lom lom zem thiab nws muaj txiaj ntsim zoo rau kev noj qab haus huv, prenylchalcone tau dav kawm tsis ntev los no [188]. Cov tshuaj muaj kev nyab xeeb kho mob thiab ntau yam bioactivities, suav nrog kev tiv thaiv kab mob, tiv thaiv kab mob ntshav qab zib, tshuaj tiv thaiv kab mob, tshuaj tua kab mob, thiab tshuaj tua kab mob. Nyob rau hauv xyoo tas los no, ntau cov kev tshawb fawb tau pom ntau qhov kev ua haujlwm ntawm kev tiv thaiv kabmob kheesxaws ntawm XN hauv ntsws cancer, hepatocellular carcinoma, cancer mis, leukemia, prostate cancer, pancreatic cancer, mob qog noj ntshav, mob qog noj ntshav, thiab glioblastoma cancer. Kev nthuav tawm ntawm cov qog nqaij hlav cancer rau XN inhibits lawv txoj kev loj hlob, kev tsiv teb tsaws, thiab ntxeem tau thiab hloov kho autophagy. Chalkone kuj muaj peev xwm ua rau apoptosis thiab thaiv lub voj voog ntawm tes [189-193]. Tsis tas li ntawd, chalcone induces apoptosis nyob ntawm thiab ntawm nws tus kheej ntawm kev ua haujlwm caspase thiab inhibits qog nqaij hlav cancer thiab angiogenesis [194]. Nws cov tshuaj tiv thaiv kab mob, tshuaj tua kab mob, thiab tshuaj tiv thaiv kab mob muaj feem cuam tshuam nrog cov tshuaj tiv thaiv kab mob ntawm cov tshuaj sib xyaw [195]. Prenylchalcone kuj metabolized rau 8-prenylnaringenin, lub zog tshaj plaws phytoestrogen paub txog hnub no [196].

Akt (tseem hu ua protein kinase B los yog PKB) yog ib qho tshwj xeeb serine / threonine-protein kinase thiab ib qho tseem ceeb hauv txoj hauv kev hauv xov tooj ntawm tes. Akt kev ua haujlwm tau hloov pauv hauv ntau hom mob qog noj ntshav thiab koom nrog ntau yam txheej txheem lom neeg, suav nrog kev loj hlob ntawm tes, apoptosis, transcription, tsiv teb tsaws, thiab ntxeem tau. Txhawm rau paub meej tias XN lub peev xwm los khi rau Akt, kev kawm hauv silico docking tau ua tiav siv Schrodinger Suite 2015 software. Cov dej molecules raug tshem tawm, thiab pH rau hydrogen atoms suav tias yog 7. Ib qho chaw ATP bind-ing tau tsim los rau kev kawm docking. XN tau npaj rau docking thaum tsis muaj qhov tsis muaj kev siv LigPrep program. Tom qab ntawd, docking cov kev tshawb fawb ntawm XN nrog Aktl thiab Akt2 tau nrog los ntawm qhov tsis tuaj yeem siv cov txheej txheem ntawm qhov tseeb ntxiv nrog Glide program txhawm rau kom tau txais cov qauv zoo tshaj plaws. Cov txiaj ntsig ntawm kev tshawb fawb docking qhia tias XN tsim cov ntawv cog lus hydrogen nrog Ala230, Glu228, Glu234, thiab Lys158 ntawm Akt1 thiab nrog Glu236, Thr213, thiab Lvs181 ntawm Akt2. Xenograft (PDX) qauv tau txheeb xyuas los txhais cov kev tshawb fawb txog kev tshawb fawb hauv kev siv tshuaj kho mob. Raws li qhov nce ntxiv, cov yam ntxwv ntawm cov kab mob lom neeg thiab cov noob caj noob ces ntawm cov neeg mob pub dawb tau suav tias yog khaws cia los ntawm cov qauv PDX, uas yog qhov zoo tshaj plaws ntawm cov qauv ntawm tes. PDX qauv tau siv los txheeb xyuas biomarkers thiab kwv yees cov lus teb rau XN kho hauv kev sim tshuaj. Chemopreventive teebmeem ntawm prenylchalcone tau muab piv raws li qib Akt. Cov txiaj ntsig tau pom tias cov qauv qog qhia txog qib siab ntawm Akt muaj qhov txo qis hauv cov qog thiab qhov hnyav thaum kho nrog XN [197]. Guo et al. kawm hauv vitro thiab vivo cov txiaj ntsig ntawm XN hauv plab hnyuv, qhia tias prenylchalcone induces apoptosis los ntawm activating caspases, tswj Bcl-2, thiab cuam tshuam PI3K/Akt/mTOR kinase. XN inhibits kev muaj peev xwm ntawm cov qog nqaij hlav hauv plab nyob rau hauv qhov concentration-dependent yam. Ntawm cov kab ntawm tes, flavonoid ua rau muaj txiaj ntsig zoo tshaj plaws ntawm kev muaj peev xwm ntawm SGC-7901 hlwb thiab tsis cuam tshuam qhov ntsuas no ntawm GES-1 hlwb ntawm 6, 8, thiab 10 ug / mL ntawm chalcone. Los ntawm kev soj ntsuam cytometric ntws, nws tau pom tias prenylchalon ua rau muaj cov hlwb apoptotic hauv plab hnyuv. Cov nyhuv ntawm XN ntawm pro-thiab anti-apoptotic proteins tau qhia los ntawm Western blot tsom. Bcl -2 thiab Bcl-XL cov protein ntau tau txo qis tom qab kev tswj hwm flavonoid, qhov kev txo qis no cuam tshuam nrog kev tswj hwm cov concentration. XN kuj nce qib Bax thiab Bid protein ntau, nrog rau kev ua haujlwm zoo tshaj plaws tau pom zoo rau 10 uM / mL ntawm chalcone. Tsis tas li ntawd, theem ntawm cleaved caspase 3 thiab cleaved PARP protein tau nce ntau heev thaum muaj chalcone. Rau cov laj thawj no, nws tuaj yeem hais tias flavonoids nyiam thiab cuam tshuam rau qib pro- thiab anti-apoptotic proteins. Tag nrho ntawm 10 uM/mL ntawm XN induces apoptosis tseem ceeb ntawm SGC-7901 hlwb. Tag nrho ntawm 8 thiab 6 uM / mL ntawm chalcone induces apoptosis ntawm 34 ± 3 feem pua ​​​​cov hlwb thiab 23 ± 2 feem pua ​​​​ntawm cov hlwb, feem. Tsis tas li ntawd, flavonoid hloov pauv phosphorylation ntawm PI3K, Akt, thiab mTOR nce qib ntawm p-PTEM thiab txo qis p-Akt (Thr308), p-Akt (Ser473), thiab m-Tor (Ser2448). Cov ntaub ntawv tshwm sim qhia tias prenylchalcone tsis cuam tshuam rau Akt, PTEN, GSK-3 , thiab mTOR theem. Kev txiav txim siab hauv SGC7901xenograft nas tau pom tias kev kho XN txo cov qog nqaij hlav hauv qhov tseem ceeb-raws li. Txhawm rau kom paub meej tias kev tawm tsam ntawm PI3K / Akt signaling hauv vivo, phosphorylated Akt thiab mTOR qhia ntawm cov qog xenographic tau soj ntsuam. Pathological kev kuaj ntawm hematoxylin thiab eosin seem qhia pom qhov txawv txav ntawm morphological. Txawm li cas los xij, XN txo cov concentration-dependent phosphorylated Akt thiab mTOR qib. Kev kho mob Prenylchalcone txo qis cell proliferation thiab nce qog cell apoptosis piv nrog cov tswj hlwb [198].

XN, ntawm qhov siab tshaj 10 umol/L, inhibits kev loj hlob ntawm pancreatic cancer hlwb hauv vitro. Ntawm qhov concentrations qis dua 5 umol / L, chalcone inhibits NF-kB-dependent angiogenic kev ua haujlwm hauv cov qog nqaij hlav qog nqaij hlav pancreatic. Ntawm qhov kev xav no, tsis muaj cytotoxicity tau pom ntawm pancreatic hlwb los ntawm WST-1 txoj kev. Txawm li cas los xij, qhov xaus ntawm txoj kev tshawb no yog tias XN cuam tshuam rau pancreatic-cancer-induced angiogenesis los ntawm downregulating zus tau tej cov VEGF thiab IL-8 (ib qho interleukin), uas yog tshwj xeeb thiab kho los ntawm NF-kB inactivation [194]. soj ntsuam XN's anticancer kev ua ub no, HepG2 cell kab tau raug rau MTT tsom xam los txiav txim qhov loj ntawm cell. Prenylchalcone txo cell proliferation nyob ntawm qhov concentration thiab lub sij hawm. Zhao et al. pom tias kev nthuav tawm cov kab ntawm tes rau 200 μM ntawm XN rau ib hnub tsis zoo dua piv nrog kev kho lawv nrog 100-200 μM ntawm chalcone rau 2-3 hnub. Ntawm 50 uM ntawm chalcone, tseem ceeb inhibition ntawm HepG2 cell proliferation tau pom tom qab 3 hnub. Hauv tib txoj kev tshawb fawb, nws tau pom tias prenylchalcone ua rau muaj kev nce ntxiv hauv caspase 3 kev ua haujlwm. Tsis tas li ntawd, los ntawm Western blot tsom xam, nws tau pom tias 100-150 uM ntawm XN cuam tshuam qhov kev qhia ntawm NF-kBprotein ntawm cov kab ntawm tes. Los ntawm qhov kev tshuaj ntsuam no, nws kuj tau pom tias prenylchalcone muaj peev xwm nce qhov kev qhia ntawm p53 protein, thiab 20 uM ntawm XN tau txiav txim siab qhov kev siv zog ntawm Bax signaling, qhov no tau cuam tshuam nrog lub sijhawm [199]. Kev tshawb fawb txog kev nyab xeeb profile ntawm XN qhia tau hais tias 1000 mg / kg ntawm cov tshuaj tsis hloov cov haujlwm ntawm lub cev tseem ceeb thiab homeostasis hauv cov nas. Prenylchalcone muaj peev xwm ua kom IL-2 ntau lawm hauv T hlwb, uas qhia tau hais tias nws muaj peev xwm los txhawb lub cev tiv thaiv kab mob. XN kuj inhibits -12. uas indirectly tsim kev sib txawv ntawm cov hlwb nyob rau hauv lub cev tiv thaiv kab mob los ntawm activating transcription molecules. CytotoxicTlymphocytes yog ib hom cellular effector tseem ceeb heev rau kev tiv thaiv ntawm tes thiab ua lub luag haujlwm tseem ceeb hauv cov txheej txheem ntawm kev tiv thaiv kab mob. CD8 ntxiv rau T cytotoxic lymphocytes muaj xws li CTL-P, ib qho tsis muaj zog ntawm tes ua ntej hauv vivo. Qhov no precursor yog qhib los ntawm antigen nyob rau hauv lub xub ntiag ntawm Th1 cytokines thiab ces loj hlob mus rau hauv mature cytotoxic T lymphocytes. Kev nce ntxiv hauv CD8 ntxiv / CD25 ntxiv tau pom, ua raws li kev hloov pauv ntawm Th2 mus rau Th1 hauv qog microclimate. CD8 ntxiv / CD25 * piv ntawm T hlwb tau nce zoo heev thaum cytotoxic T lymphocytes tau qhib los ntawm CoCl2 ntawm 4T1 cell kab. Kev ua haujlwm ntawm Th1 thiab Th2 hlwb yog nyob ntawm qhov tso tawm ntawm ntau yam cytokines. Txhawm rau tshawb xyuas cov teebmeem ntawm XN ntawm Th1 thiab Th2 cytokines, Zhang et al. txiav txim siab qib ntshav ntawm Th1l thiab Th2- koom nrog cytokines siv cov khoom siv ELISA. Prenyl derivative tau pom tias nce Th1 cytokine qhia ntau (xws li IL-2 thiab IFN-y) thiab txo Th2 cytokine theem (xws li IL-4 thiab IL-10). Qhov kev txiav txim siab no tau piav qhia los ntawm qhov tseeb tias Th1 thiab Th2 yog kev sib koom ua ke. Tsis tas li ntawd, qhov sib piv Th1 / Th2 tau txiav txim siab los ntawm kev ntws cytometry, qhia tias nws tau nce ntau los ntawm XN. Cov kev tshawb fawb zoo sib xws tau tshaj tawm qhov kev tshawb pom no rau ntau yam qog. Cov neeg mob uas muaj cov kab mob squamous cell carcinomas ntawm lub caj dab thiab lub taub hau muaj cov theem qis ntawm Th1 cytokines piv nrog cov neeg mob uas tsis tshua muaj mob hnyav thiab muaj qib siab ntawm Th2 cytokines. Kev sib xyaw ua ke ua rau kev hloov pauv ntawm Th2 mus rau Th1 cytokines hauv cov qog nqaij hlav. Cov txiaj ntsig ntawm kev tshawb fawb qhia tau hais tias muaj kev cuam tshuam ntawm Th1 / Th2 cytokine piv, qhov kev hloov pauv no tau pom rau ntau hom qog nqaij hlav, feem ntau nyob rau theem kawg ntawm kev mob qog noj ntshav. Txhawm rau kom paub meej tias qhov muaj peev xwm ntawm XN ntawm Thl / 'Th2 cytokine piv, qhov kev qhia ntawm qhov tseem ceeb hauv txoj hauv kev ntawm Th1 thiab Th2 sib txawv tau txiav txim siab. Physiologically, Th0 hlwb yog proportionally sib txawv rau Thl thiab Th2 hlwb. Tsis tas li ntawd, kev ua kom muaj kev hloov pauv ntawm cov molecules 4 thiab 6 ua lub luag haujlwm tseem ceeb hauv kev sib txawv ntawm Th0 rau Th1 thiab Th2 hlwb. T-bet thiab GATA-3 kuj ua ob lub luag haujlwm tseem ceeb. CpG-ODN (cytosine-phosphorothioate-guanine muaj ib qho oligodeoxynucleotide), muaj zog Th1 adjuvant, txo GATA-3 kev qhia thiab ua kom cov transcriptional molecule 6 los ntawm activating T-bet thiab transcriptional molecules 1 thiab 4 nyob rau hauv lub ntsws qauv. XN nce T-bet qhia thiab txo GATA-3 qhia. Ua kom cov transcriptional molecule 4 yog nce nyob rau hauv lub xub ntiag ntawm XN, tab sis nws tsis cuam tshuam rau lub activation ntawm transcriptional molecule 6. Vim li no, nws muaj peev xwm hais tau hais tias activation ntawm transcriptional molecule 4 plays lub luag hauj lwm zoo nyob rau hauv regulating Th1/Th2 cytokine. piv los ntawm XN [200].

Txoj kev taw qhia txoj hauv kev ua lub luag haujlwm tseem ceeb hauv kev mob qog noj ntshav mis, uas yog lub hom phiaj kho mob rau nws txoj kev kho mob. Nws koom nrog hauv kev pib thiab kev loj hlob ntawm mob qog noj ntshav mis, kev ua haujlwm tsis zoo ntawm txoj kev no tau cuam tshuam nrog cov kab mob no. Inhibition of Notch signaling pathway by gamma-secretase inhibitors thiab los ntawm anti-delta-zoo li monoclonal antibody 4 yog qhov zoo rau kev kho mob ntawm lymphoblastic leukemia thiab cov qog nqaij hlav. Mechanisms ntawm cov neeg ua hauj lwm muaj xws li cell cycle blockage los yog apoptosis thiab cuam tshuam ntawm angiogenesis. Sun et al. tshawb xyuas cov peev xwm kho tau ntawm XN ntawm cov kab mob qog noj ntshav ntawm lub mis, qhia txog nws lub peev xwm los cuam tshuam cov cell proliferation, thaiv lub voj voog ntawm tes, thiab induce apoptosis hauv vitro. Kev txo cov qog loj hlob hauv vivo kuj tau txiav txim siab. Tsis tas li ntawd, qhov muaj peev xwm ntawm prenylchalcone los tiv thaiv kev loj hlob ntawm tib neeg cov qog nqaij hlav qog noj ntshav los ntawm Notch signaling pathway tau tshawb xyuas. Txhawm rau txiav txim siab seb XN lub hom phiaj rau txoj hauv kev taw qhia txoj hauv kev, ib txoj kev ua haujlwm Notch 1 tau siv, siv gamma-secretase inhibitor (DAPT) ua tus tswj. Lub hom phiaj ntawm txoj kev tshawb no yog los soj ntsuam qhov ua tau tias prenylchalcone txo cov kev sib txuas ntawm Notch1 rau CBF1 transgene. XN tau pom tias inhibit proliferation thiab induce apoptosis los ntawm inhibiting txoj kev Notch 1. Tsis tas li ntawd, los ntawm MTT txoj kev thiab lub teeb microscopy, nws tau pom tias prenylchalkone inhibits cell proliferation ntawm cov kab mob qog noj ntshav ntawm lub mis. Cov kev tshawb fawb yav dhau los tau qhia tias Notch pathway inhibitors kuj yog cov inhibitors ntawm EGFR qhia, lwm qhov ua rau mob qog noj ntshav. Tsis tas li ntawd, XN ua rau cov proteins cuam tshuam nrog qog nqaij hlav metastases thiab inhibits cell migration los ntawm kev nthuav qhia cov proteins. Ib txoj kev tshawb fawb qhia txog kev thaiv ntawm lub voj voog ntawm tes hauv G0/G1 theem thiab induction ntawm apoptosis rau MCF{11}} thiab MDA-MB-231 hlwb los ntawm XN [201].

3.1.7.Panduretin A

AnticancerKev ua ntawm pandurate A (PA, Tables S1, thiab S2, compound 7), cyclohexanylchalcone cais los ntawm Boesenbergia pandurate, tau kawm. Cov nroj tsuag muaj prenyl chalcones thiab lwm yam flavonoids uas yog bioactive molecules loj, uas tau piav nyob rau hauv cov ntaub ntawv kom muaj kev nyiam cytotoxic zog ntawm tib neeg pancreatic cell kab PANC-1. [202,203] PA ua haujlwm hauv melanoma, colon adenocarcinoma, thiab mob qog noj ntshav prostate. Proteomic tsom xam qhia tias PA muaj cytotoxicity ntawm melanoma hlwb uas nyob ntawm denaturation ntawm mitochondrial oxidative phosphorylation txheej txheem, nrog rau cov kev ua ntawm secretory pathway thiab apoptosis induced los ntawm oxidative dab. Hauv qhov no, nws tau pom tias oxidative kev nyuaj siab tuaj yeem yog qhov tshwm sim ntawm kev txhawb nqa autophagy raws li cov lus teb thib ob rau siab ROS [204]. Cov ntaub ntawv qhia tias qhov concentration ntawm 9 ug / mL ntawm PA tag nrho inhibits kev loj hlob ntawm MCF-7 hlwb thiab HT-29 hlwb (ib kab mob qog nqaij hlav hauv tib neeg)[205]. Cov chalcone muaj cov tshuaj tiv thaiv kab mob ntawm ntau hom cell, suav nrog melanoma, colon adenocarcinoma, thiab prostate cancer [204]. Liu et al. qhia txog cov txiaj ntsig cytotoxic ntawm chalcone ntawm MCF-7, T47D (tib neeg mob qog noj ntshav), thiab MCF-10A (tsis yog qog nqaij hlav hauv mis) cov kab ntawm tes. IC50 qhov tseem ceeb ntawm PA ntawm MCF{17}} hlwb yog 15 uM ntawm 24h thiab 11.5 μM ntawm 48 h.Rau cov T47D hlwb, IC50 yog 17.5 μM ntawm 24h thiab 14.5 μM ntawm 48 h. PA tsis cuam tshuam rau kev loj hlob ntawm MCF-10A cell. Txhawm rau txheeb xyuas cov txheej txheem uas cov chalcone induces cell cycle blockade in MCF-7 cells nyob rau theem GO/G1, Western blot tsom tau siv, uas yog siv los ntsuas qhov kev hloov pauv ntawm kev tswj hwm cov protein hauv lub voj voog ntawm tes. Cov txiaj ntsig tau pom tias kev kho PA ua rau txo qis hauv cyclin D1 thiab CDK4 kev nthuav qhia thiab nce p21Cip1 thiab p27 qhia, yog li piav qhia txog kev thaiv hauv theem G0 / Gl. Cais PA los ntawm Kaempferia pandurate induces cell cycle blockade in androgen-independent PC-3 (prostate adenocarcinoma) cells thiab in human DU145 ( human prostate cancer cell line) cells. Internucleosomal DNA fragmentation yog ib qho cim ntawm apoptosis. Vim tias tsis muaj molecular-yeeb DNA tawg yog muab rho tawm los ntawm cov staining hlwb nyob rau hauv aqueous daws, apoptotic hlwb yuav raug txheeb xyuas los ntawm zaus histograms ntawm DNA cov ntsiab lus nyob rau hauv daim ntawv ntawm cov hlwb nrog fractionated DNA cov ntsiab lus. Ib sub-G1 theem MCF-7 cov pejxeem tau txheeb xyuas. G1 theem cov ntsiab lus ntawm cov hlwb yog 1.17 ± 0.11 thiab hauv cov hlwb kho nrog PA (10,15, thiab 20 μM) nws yog 1.84 ± 0.18, 2.62 ± 0.21, thiab 4.52 ± 0.28, feem. Qhov nce hauv kev kho chalcone yog vim qhov hnyav ntawm DNA fragmentation ntawm MCF-7 kab, qhov tseeb tau lees paub los ntawm sub-G1 theem ntawm cov cell [206].

Ntawm cov proteins tseem ceeb ntawm kev mob qog noj ntshav thiab cov kab mob metastasis, induction yog matrix metalloproteinases. Lawv degrade cov khoom ntawm extracellular matrix thiab pab txhawb kev ntxeem tau thiab tsiv teb tsaws ntawm cov hlwb. Tsis tas li ntawd, overexpression ntawm metalloproteinases tuaj yeem ua rau muaj kev hloov pauv ntawm epithelial-mesenchymal. PA inhibits lub secretion thiab ua kom cov metalloproteinase 2, ua rau inhibition ntawm endothelial cell migration, ntxeem tau, thiab morphogenesis ntawm tib neeg umbilical leeg endothelial cell (HUVEC) cell. Tsis tas li ntawd, cov tshuaj subtoxic ntawm chalcones txaus los txo qis metalloproteinase 2 hauv cov qog nqaij hlav ntsws [207].

3.1.8 ib. Cardamonin

Cardamon (CD, Tables S1, thiab S2, compound 8), chalcone los ntawm Campomanesia adamantium (Myrtaceae), nce DNA fragmentation thiab txo NF-kB kev ua haujlwm hauv PC-3 hlwb. Cov txiaj ntsig no qhia txog kev kho lub peev xwm ntawm chalcone hauv kev kho mob qog noj ntshav prostate [20]. CD yog suav tias yog ib qho ntawm cov tshuaj tiv thaiv kab mob siab tshaj plaws uas ua kom tus kab mob Epstein-Barr koom nrog [208]. Anticancer teebmeem ntawm CD yog cuam tshuam nrog induction ntawm apoptosis, inhibition ntawm cell proliferation thiab migration, thiab muaj feem xyuam rau lub voj voog ntawm tes. Lub chalcone kuj muaj peev xwm txo tau qhov tsis kam ntawm cov qog nqaij hlav cancer rau kev kho. Hauv kev sib xyaw nrog 5-fluorouracil lossis cis-platinum, tau txais cov kev ua ub no ntau ntxiv. Piv txwv li, CD muaj peev xwm ua kom muaj peev xwm tiv thaiv kev tiv thaiv kev kho mob ntawm cov kab mob qog noj ntshav hauv plab, induces apoptosis, activates caspases 3 thiab 9, txhawb nqa Bax protein qhia, cuam tshuam c-myc, thiab nqa tshwj xeeb 50 thiab NF-kB [209. ]. Hou et al. tshawb xyuas cov peev xwm kho mob thiab cov txheej txheem molecular ntawm CD ntawm 5-fluorouracil-resistant gastric cells. Qhov rhiab heev ntawm BGC{18}}/5-fluorouracil rau 5-fluorouracil tau lees paub los ntawm kev nce apoptosis thiab thaiv lub voj voog ntawm tes ntawm CD. Cov chalcone ua rau kom muaj kev nkag siab ntawm cov qog nqaij hlav cancer rau 5- fluorouracil los ntawm kev ua rau Wnt / -catenin signaling txoj hauv kev (uas ua lub luag haujlwm tseem ceeb hauv cov qog nqaij hlav), thiab ua kom muaj kev hloov pauv hauv Wnt / -catenin noob tau cuam tshuam nrog kev tiv thaiv kev kho mob qog noj ntshav. . Nws inhibits kev qhia ntawm P-glycoprotein, -catenin, thiab TCF-4. Tsis tas li ntawd, CD tshwj xeeb thaiv kev tsim ntawm -catenin / TCF-4 complex, yog li ua rau tsis zoo Wnt / -catenin signaling [210]. Chav pw et al. tshawb xyuas cov tshuaj tiv thaiv kab mob thiab apoptotic cuam tshuam ntawm CD ntawm HepG2 hlwb. Qhov inhibitory kev ua ntawm

cov chalcone ntawm HepG2 cell proliferation yog qhov tseem ceeb tom qab 72 h, cytotoxicity zoo ib yam li ntawm 5-fluorouracil. Cov txiaj ntsig tau txiav txim siab rau lwm cov tshuaj kws khomob uas siv los ua cov qauv (xws li sorafenib) qis dua. Tsis tas li ntawd, cov nyhuv cytotoxic ntawm cov khoom sib xyaw yog xaiv ntawm cov qog hlwb thiab tsis ua rau lub cev tsis zoo, uas yog qhov zoo ntawm CD piv nrog 5-fluorouracil. Kev sib sau ntawm CD hauv G1 theem ntawm lub voj voog ntawm tes tau pom tom qab 72 h thiab qhia tias inhibition ntawm HepG2 cell loj hlob los ntawm kev tiv thaiv cell division [211].

Kev sib piv docking kev tshawb fawb ntawm CD thiab 5-fluorouracil thiab nws cov kev cuam tshuam nrog BaxBH3 qhia tau hais tias 5-fluorouracil muaj zog khi dua li CD. Cov chalcone tsim peb daim ntawv cog lus hydrogen (Phe30, Val50, thiab Gln52). Kev sib cuam tshuam ntawm CD thiab Bcl yog ua tiav los ntawm peb daim ntawv cog lus hydrogen (Asp15, Gln18, thiab Ser28), thiab nyob rau hauv rooj plaub ntawm 5-fluorouracil yog ua tiav los ntawm plaub daim ntawv cog lus. Tsis tas li ntawd, nyob rau hauv rooj plaub ntawm qhov kev cuam tshuam no, lub zog khi ntawm CD yog qis dua li ntawm 5-fluorouracil. Qhov no tuaj yeem raug ntaus nqi rau cov ntxhiab tsw qab nyob rau hauv cov qauv ntawm cov chalcone, uas muaj kev koom tes hauv II daim ntawv cog lus, uas muaj peev xwm ua kom ruaj khov ntawm lub hnab tshos nquag thiab ua rau txo qis hauv kev khi lub zog. Cov txiaj ntsig ntawm kev tshawb fawb silico qhia tau tias 5-fluorouracil muaj zog khi ntau dua li caspase 3 piv nrog CD.CDs qhia ob daim ntawv cog lus hydrogen hauv kev cuam tshuam nrog caspase 3 (Cys163 thiab Arg64). Lub chalcone kuj muaj II-II daim ntawv cog lus nrog TYR204. Lub zog ruaj khov ntawm 5-fluorouracil yog qhov zoo tshaj plaws ntawm CD, uas tau piav qhia los ntawm kev ruaj khov ntawm lub hnab tshos nquag los ntawm ob qho chaw uas muaj ntxhiab nyob hauv cov qauv ntawm chalcone [212].

3.1.9. Lonchocarpin

Lonchocarpin (Tables S1 thiab S2, compound 9) yog lub ntuj chalcone rho tawm los ntawm Lonchiocarpus sericeus. Cov teebmeem cytotoxic ntawm cov chalcone no tau piav qhia txog cov kab mob neuroblastoma thiab leukemia cell kab. Nws paub tias 24h tom qab kev kho mob nrog 50 uM lonchocarpin ntawm SK-N-SH neuroblastoma kab, induction ntawm AMPK phosphorylation tshwm sim, uas ua rau kom cov piam thaj nqus thiab inhibits protein synthesis. Lub chalcone kuj muaj peev xwm txo qis cell viability. Ntawm kab mob qog nqaij hlav hauv plab HCT116, SW480, thiab DLD, lonchocarpin txo cov cell viability los ntawm 20μM. Cov kev tshawb fawb pom tau tias lonchocarpin muaj peev xwm inhibit H292 mob ntsws cancer hlwb hauv vitro los ntawm caspase{11}}induced cell tuag uas ua ntej apoptosis. Tsis tas li ntawd, lonchocarpin tau pom tias inhibit Wnt / -catenin signaling hauv vivo hauv cov qauv embryonic ntawm Xenopus laevis. Lub chalcone txhaj rau hauv ib qho kev txhaj tshuaj Wnt8-cov qauv tshwj xeeb receptor (SO1234) ua rau 82 feem pua ​​​​tawm ntawm Wnt / -catenin signaling receptor gene activation [213].

Hauv kev tshawb fawb los ntawm Chen li al., cov txiaj ntsig ntawm 3D-QSAR tsom xam qhia tias hydrophobic C-4, C-5, C-11, C-1/, thiab C -2 kev sib cuam tshuam hauv lonchocarpin. Qhov kev sib cuam tshuam no nce lub peev xwm cytotoxic ntawm qhov sib xyaw no, muaj kev koom tes ntawm 23 feem pua ​​​​hauv cov qauv. Cov kev tshawb fawb docking rau lonchocarpin tau txais txiaj ntsig zoo ib yam li cov qauv hydrophobic 3D-QSAR, nrog rau qhov chaw hydrophobic hauv C-4, C-5, C-11, C-1' , thiab C-2'regions of loncocarpine interacting with the Bcl-2 complex. Lub voj hydrophobic ntawm Bcl -2 cov protein ua ib txoj hauv kev nrog BaxBH3 peptide, uas tuaj yeem cuam tshuam los ntawm hluavtaws navitoclax lossis lonchocarpin compounds. Qhov no qhia tau hais tias lub voj hydrophobic ntawm Bcl -2 cov neeg hauv tsev neeg yog lub hom phiaj rau loncocarpine-induced apoptosis ntawm H292 hlwb thiab yog li ua kom cov caspase 3 [214].

Lwm yam ntuj chalcones nrog anticancer zog yog butein (Tables S1 thiab S2 compound 10), isoliquiritigenin (Tables S1 thiab S2, compound 11), flavokawain (Tables S1 thiab S2, compound 12), thiab isobavachalcone (Tables S1 thiab S2, compound 13) [155].

Nyem qhov link kom tau qhov 3:https://www.xjcistanche.com/news/part3-anticancer-activity-of-natural-and-synt-54978140.html