Cistanche Tubulosa Induces Reactive Oxygen Species-mediated Apoptosis Ntawm Thawj Thiab Metastatic Tib Neeg Colon Cancer Cells
Feb 23, 2023
TSAB NTAWV
Colon cancer yog thib peb feem ntau mob qog noj ntshav thoob ntiaj teb. Cov kev kho mob ib txwm tau pom tias muaj kev ua tau zoo me ntsis nrog cov kev cuam tshuam loj heev, yog li muaj kev xav tau sai dua rau kev nyab xeeb dua. Nyob rau hauv txoj kev tshawb no, Cistanche tubulosa, lub zos lub npe Thanoon, raug suav hais tias yog ib tug muaj peev xwm phytotherapeutic lub tswv yim vim hais tias ntawm nws lub npe hu muaj peev xwm kho tau zoo nyob rau hauv cov tshuaj ib txwm siv thiab dav abundance nyob rau hauv Middle East cheeb tsam. Bioactive compounds tau muab rho tawm los ntawm cov hmoov Cistanche tubulosa thiab kuaj rau lawv cov khoom tiv thaiv kab mob tiv thaiv plaub kab mob qog noj ntshav nrog rau ob qhov muab tau los ntawm cov qog thawj (CaCo2 thiab HCT116) thiab ob qhov muab tau los ntawm qhov chaw metastatic (LoVo thiab SW620).
Cov txiaj ntsig ntawm Cistanche tubulosa ntawm induction ntawm apoptosis thiab cellular redox homeostasis kuj tau tshawb xyuas. Cistanche tubulosa tau nthuav tawm qhov concentration thiab lub sij hawm-nyob ntawm qhov inhibition ntawm kev loj hlob ntawm tag nrho cov kab mob qog noj ntshav tau kuaj los ntawm ntau dua 60 feem pua ntawm 72 teev ntawm kev kho mob nrog 1 mg / mL ntawm crude extract. Inhibition ntawm proliferation tau cim los ntawm induction ntawm apoptosis, intracellular reactive oxygen hom tsim, thiab mitochondrial superoxides. Cov ntaub ntawv no qhia tau hais tias Cistanche tubulosa yog ib tus neeg sib tw ua tau zoo rau kev kho mob qog noj ntshav ntxiv. Qhov no yog thawj txoj kev tshawb fawb qhia txog kev tiv thaiv kab mob qog noj ntshav ntawm Cistanche tubulosa tiv thaiv kab mob qog noj ntshav.
Nyem tshuaj kho ntawm cistanche cog extract khoom
Cov ntawv luv:
7-AAD, 7-Amino-Actinomycin D; CTE, Cistanche tubulosa extract; EMEM, Eagle qhov tsawg kawg nkaus qhov nruab nrab; FBS, fetal bovine serum; DCF, 2, 7-dichlorofluorescein; DCFH-DA, 2, 7- dichlorodihydrofluorescein diacetate; DMEM, Dulbecco's Modified Eagle's Medium; DMSO, dimethylsulfoxide; MTT, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium; PE, Phycoerythrin; RFU, txheeb ze fluorescence units; ROS, reactive oxygen hom

Taw qhia
Kev mob qog nqaij hlav hauv plab yog ib qho mob qog noj ntshav thoob plaws ntiaj teb (Brenner li al., 2014), thiab nws qhov xwm txheej tau nce ntxiv nrog kwv yees li 2.4 lab tus neeg nyob rau xyoo 2035, vim muaj kev noj haus niaj hnub thiab kev ua neej nyob, nrog rau kev txo qis hauv lub cev. Cov kev siv zog tam sim no tsis txaus los tawm tsam cov kab mob qog nqaij hlav hauv plab tam sim no thiab yog li yuav tsum muaj cov txheej txheem tshiab rau kev tiv thaiv thiab kev kho mob nrog rau kev hloov hauv kev ua neej nrog rau lwm txoj kev nyab xeeb xws li Phytotherapeutics (Weidner li al., 2015). Phytotherapy, kev siv cov nroj tsuag tshuaj los kho cov kab mob, tau ua ib feem ntawm tib neeg keeb kwm yav dhau los. Cov nroj tsuag tshuaj tau ntev tau siv los ua lwm txoj hauv kev kho mob qog noj ntshav, sawv cev ntau dua li rau caum feem pua ntawm cov tshuaj tiv thaiv kab mob uas siv hauv cov tshuaj (Balunas thiab Kinghorn, 2005; Saibu et al., 2015). Qee qhov piv txwv zoo tshaj plaws suav nrog cov extracts ntawm Catharanthus roseus G. Don. (Apocynaceae), Taxus baccata L. (Taxaceae), thiab Camptotheca acuminate Decne (Nyssaceae) (Cragg and Newman, 2005; da Rocha et al., 2001). Ntau cov tshuaj ntsuab rho tawm thiab phytochemicals tau pom tias ua rau muaj kev cuam tshuam los ntawm kev mob qog noj ntshav hauv cov qog nqaij hlav hauv plab vim yog qhov cuam tshuam ntawm cov pa oxygen reactive (ROS) ntau lawm thiab cuam tshuam apoptosis ntawm cov qog nqaij hlav cancer xws li hauv cov ntaub ntawv rho tawm los ntawm Melissa officinalis (Weidner li al., 2015).
Ntawm cov phytotherapeutic neeg sib tw, Cistanche tubulosa, Orobanchaceae parasitic suab puam tsob nroj (Jiang li al., 2009) uas yog dav faib nyob rau hauv arid thiab ib nrab arid cheeb tsam ntawm teb chaws Africa, Asia, thiab Mediterranean cheeb tsam, tau pom tias muaj nuj nqis tshuaj muaj txiaj ntsig. Cistanche tubulosa tau siv dav hauv cov tshuaj ib txwm siv thiab pom zoo kom muaj kev kho mob hauv lub raum tsis txaus, mob leucorrhea, metrorrhagia, poj niam muaj menyuam, thiab cem quav (Jiang li al., 2009). Cov khoom ntawm Cistanche Tubulosa tau raug tshawb fawb ntau thaum lub xyoo caum dhau los suav nrog vasorelaxant (Yoshikawa li al., 2006), hepatoprotective (Morikawa li al, 2010), los tiv thaiv hyperglycemic thiab hypolipidemic teebmeem (Xiong li al., 2013). Cistanche Tubulosa kuj tau pom zoo tias yog lub zog txhawb zog ntawm lub cev tiv thaiv kab mob, txhawb kev tsim cov pob txha, thiab cov tshuaj tiv thaiv kev laus thiab kev qaug zog (Xu li al., 2014). Tsis tas li ntawd, Cistanche tubulosa extract tau pom tias thaiv amyloid deposition hauv Alzheimer tus kab mob qauv (Wu li al., 2015). Txawm hais tias nws siv ntau yam kev kho mob, cov txiaj ntsig ntawm Cistanche Tubulosa ua tus neeg sawv cev tiv thaiv kab mob tseem tsis tau kawm.
Hauv kev ua haujlwm tam sim no, peb tau tshawb xyuas cov nyhuv anticancer ntawm Cistanche Tubulosa ntawm ob lub hauv paus thiab ob txoj kab mob qog noj ntshav hauv cov kab mob metastatic thiab cov txheej txheem muaj peev xwm hauv qab no.

Cov khoom siv thiab cov txheej txheem
Kev sau thiab kev npaj cov nroj tsuag extract, cov qauv ntawm Cistanche tubulosa tau sau los ntawm thaj chaw suab puam hauv Qatar hauv 2014 thiab qhov tseeb ntawm cov nroj tsuag tau lees paub los ntawm kws kho tsiaj. Cov qauv Voucher tau khaws cia hauv Toxicology thiab Multipurpose Department ntawm ADLQ. Cov nroj tsuag sundried tau hauv av nrog Retsch Riam Mill Grindomix GM300 rau hauv cov hmoov zoo. Nees nkaum grams hmoov tau muab rho tawm nrog 200 mL ultrapure dej thaum hmo ntuj ntawm 37 degree ntawm lub teb shaker ntawm 200 rpm. Cov khoom nyoos Cistanche tubulosa extracts (CTE) tau centrifuged rau 30 min ntawm 8000 rpm rau pellet nonsoluble compounds, supernatant sau, thiab khov-dried siv Labconco Freezone 6 plus Freeze dryer. Cov extract qhuav tau rov tsim dua tshiab hauv Dulbecco's Modified Eagle's Medium (DMEM, SIGMA, Lub teb chaws Yelemees) mus rau qhov concentration ntawm 20 mg / mL thiab sterile-filtered los ntawm 0.2-micron membrane lim.
Cell kab thiab kev kho ntawm tes
Tib neeg txoj hnyuv carcinoma cell kab CaCo2, SW620, thiab LoVo tau txais los ntawm Cell Lines Service (CLS, Eppelheim, Lub teb chaws Yelemees) thaum HCT 116 cell kab yog ib yam khoom plig los ntawm Biological thiab Environmental Sciences, Department ntawm Qatar University. CaCo2 thiab HCT11 tau muab los ntawm thawj qhov chaw ntawm txoj hnyuv loj thaum SW620 thiab LoVo tau muab los ntawm qhov chaw metastatic. SW620, HCT116, thiab LoVo hlwb raug coj mus kuaj thiab khaws cia hauv DME Nruab Nrab thaum CaCo2 hlwb tau khaws cia hauv Eagle Qhov Tseem Ceeb Tsawg Nruab Nrab (EMEM, SIGMA, Lub Tebchaws Yelemees). Cov hlwb tau loj hlob raws li monolayer kab lis kev cai ntawm 37 degree nyob rau hauv nruab nrab nruab nrab ntxiv nrog 10 feem pua fetal bovine serum (FBS, SIGMA, Lub teb chaws Yelemees) thiab 1 feem pua Penicillin / Streptomycin (SIGMA, Lub teb chaws Yelemees) nyob rau hauv ib tug humidified huab cua uas muaj 5 feem pua carbon dioxide.
Cell viability assay
Lub {{0}}[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium (MTT) assay tau siv los ntsuas cov kev ua cytotoxic ntawm CTE zoo ib yam li tau piav ua ntej (Jaganjac li al., 2010). Cov noob ntom ntom ntawm CaCo2, HCT116, SW620, thiab LoVo cells kab lis kev cai hauv 96- cov phiaj xwm zoo yog 104 lub hlwb hauv ib qhov dej. Cells tau plated nyob rau hauv cov nruab nrab nruab nrab ntxiv nrog 10 feem pua FBS 24 teev ua ntej kev kho mob. Tom qab 24 teev, qhov nruab nrab raug tshem tawm thiab cov hlwb raug kho nrog 0, 0.25, 0.5, 1, thiab 2 mg / mL ntawm CTE rau 24, 48, thiab 72 teev ntawm 37 degree hauv qhov chaw noo uas muaj 5% CO2. Thaum kho CTE, qhov nruab nrab raug tshem tawm thiab 40 µL ntawm MTT tov (0.5 mg / mL) ntxiv rau txhua qhov dej.
Tom qab 3 h ntawm incubation, cov tshuaj MTT raug tshem tawm, cov khoom formazan yaj nyob rau hauv dimethylsulfoxide (DMSO, SIGMA, lub teb chaws Yelemees), thiab lub absorbance yog ntsuas ntawm 590 nm nrog ib tug microplate nyeem ntawv (Infinite 200 PRO NanoQuant, Tecan Trading AG, Switzerland) .

Apoptosis kev xeem
Apoptosis hauv CaCo2, HCT116, SW620, thiab LoVo hlwb tau kuaj pom siv PE Annexin V Apoptosis Detection Kit I nrog 7-Amino-Actinomycin D (7-AAD) ua cov xim tseem ceeb (Becton Dickinson International, Belgium) raws li cov chaw tsim khoom cov lus qhia. Luv luv, cov hlwb tau cog rau hauv 24-cov phiaj zoo ntawm qhov ntom ntawm 5 × 104 lub hlwb / qhov zoo hauv cov xov xwm sib txuas ntxiv nrog 10 feem pua FBS rau 24 teev ua ntej qhov sib ntxiv ntawm CTE (0, 0.5 , los yog 1 mg / mL). Tom qab 24 CTE incubation, hlwb raug sau, ntxuav ob zaug nrog txias phosphate-buffered saline, thiab stained nrog Phycoerythrin (PE) Annexin V thiab 7-AAD rau 15 min ntawm chav tsev kub hauv qhov tsaus ntuj. Cov hlwb stained tau txheeb xyuas hauv 1 teev los ntawm kev ntws cytometry siv FACS. Aria III flow cytometer thiab FACSDiva software (Becton Dickinson) ntawm tus nqi qis qis nrog tsawg kawg ntawm 104 hlwb. Kev kho cov hlwb rau 4 teev nrog 6 µM camptothecin (SIGMA) tau siv los ua kev tswj xyuas qhov zoo.
Intracellular ROS ntau lawm
Intracellular ROS ntau lawm tau tshuaj xyuas siv 2, 7- dichlorodihydrofluorescein diacetate (DCFH-DA, SIGMA, Lub teb chaws Yelemees). DCFH-DA yog ib qho kev sojntsuam uas tsis muaj fluorescent, uas yog oxidized nrog intracellular ROS rau cov fluorescent compound 2, 7- dichlorofluorescein (DCF) (Poljak-Blazi li al., 2011). Qhov kev ntsuam xyuas DCFHDA tau ua zoo ib yam li peb tau piav ua ntej (Cindric li al, 2013; Poljak-Blazi li al., 2011). Luv luv, cov noob ntom ntom ntawm CaCo2, HCT116, SW620, thiab LoVo hlwb kab lis kev cai nyob rau hauv 96-zoo dub daim hlau yog 104 hlwb rau ib qhov dej. Cells raug plated nyob rau hauv nruab nrab nruab nrab ntxiv nrog 10 feem pua FBS rau 24 teev.
Ua ntej kev kho mob hlwb raug incubated nrog 10 µM DCFH-DA ntawm 37 degree rau 30 min hauv 5 feem pua CO2 / 95 feem pua ntawm huab cua. Cells ces ntxuav thiabkho nrog {{0}}, 0.5, thiab 1 mg/mL ntawm CTE hauv nruab nrab w/o phenol liab. Lub intracellular ROS tsim tau raug saib xyuas tsis tu ncua thoob plaws 25 teev ntawm 37 degree thiab 5 feem pua CO2 siv lub microplate nyeem ntawv nrog cov fluorescence sab saum toj thiab roj tswj module (Infinite 200 PRO, Tecan Trading AG, Switzerland). Qhov kev siv fluorescence tau ntsuas nrog qhov excitation wavelength ntawm 500 nm thiab emission detection ntawm 529 nm. Cov arbitrary units, cov txheeb ze fluorescence units (RFU), tau raws ncaj qha los ntawm fluorescence siv.
Mitochondrial superoxide tiam
Lub peev xwm ntawm CTE rau induce superoxide tiam los ntawm mitochondria tau kwv yees siv lub cell-permeable, mitochondria-targeted MitoSOX Red sojntsuam (Lub neej Technologies) thiab Hoechst 33342 rau nuclear staining (Life Technologies). CaCo2, HCT116, SW620, thiab LoVo hlwb tau muab noob rau hauv 96-cov phaj zoo ntawm qhov ntom ntawm 104 lub hlwb rau ib qhov dej hauv qhov nruab nrab uas ntxiv nrog 10 feem pua FBS rau 24 teev . Cells tau thauj khoom nrog 4 µM ntawm MitoSOX thiab 2 µM ntawm Hoechst 33342 rau 20 min, ntau cov tshuaj ntxuav, thiab cov dej kho nrog 0, 0.5, thiab 1 mg / mL ntawm CTE rau 24 teev ntawm 37 degree thiab 5 feem pua CO2. Qhov kev siv fluorescence tau ntsuas nrog qhov excitation wavelength ntawm 510 nm thiab emission detection ntawm 580 nm rau MitoSOX thiab ib tug excitation wavelength ntawm 350 nm thiab emission detection ntawm 461 nm rau Hoechst 33342 siv ib tug microplate nyeem ntawv nrog rau sab saum toj 2 fluorite PRO AG, Switzerland)
Kev txheeb cais
Cov txheeb cais piav qhia tau pom tias qhov nruab nrab ntxiv /- SD. Qhov tseem ceeb ntawm qhov sib txawv ntawm cov pab pawg tau raug ntsuas los ntawm Kev Ntsuas Cov Tub Ntxhais Kawm t-test thiab Chi-square test. Thaum ntau tshaj ob pawg tau muab piv, peb siv ANOVA ib sab nrog qhov tsim nyog tom qab hoc xeem. SPSS 11.01 rau Mircosoft Windows tau siv. Qhov sib txawv nrog P tsawg dua 0.05 tau suav tias yog qhov tseem ceeb.

TSEEM CEEB
Cov nyhuv ntawm CTE rau kev loj hlob ntawm tib neeg txoj hnyuv kab mob qog noj ntshav yog qhia hauv daim duab 1. Txhua qhov CTE concentrations kuaj pom muaj zog inhibitory nyhuv ntawm CaCo2 cell kab nyob rau hauv ib tug concentration thiab lub sij hawm-dependent yam (Daim duab 1A). Xya caum-ob teev ntawm CTE kev kho mob inhibited kev loj hlob ntawm CaCo2 hlwb los ntawm ntau tshaj 60 feem pua piv rau cov tswj (p < 0.05 rau tag nrho cov concentrations). Qhov cuam tshuam tseem ceeb ntawm kev kho CTE ntawm HCT116 cell loj hlob kuj tau kuaj pom ntawm txhua lub sijhawm ntawm ob qhov siab tshaj plaws (1 mg / mL thiab 2 mg / mL), ncav cuag ntau dua 70 feem pua txo ntawm qhov kawg concentration (Daim duab 1B, p. <0.05).
Txawm hais tias ob qhov qis CTE concentrations ({{0}}}.25 thiab 0.5 mg/mL) txo qis HCT116 kev loj hlob ntawm cov hlwb tom qab 24 teev (p<0.05), 72="" they="" had="" no="" significant="" effect="" following="" hours="" of="" treatment="" compared="" to="" the="" control="" p="">{{0}}}{{10}}}5). Lub sij hawm thiab concentration-dependent inhibition ntawm proliferation nrog CTE tau paub tseeb ntxiv nyob rau hauv LoVo hlwb los ntawm ntau tshaj 60 feem pua ntawm qhov siab tshaj concentration (p < 0.05) (Daim duab 1C) , thiab tag nrho plaub qhov kev ntsuas CTE txo qis kev loj hlob ntawm SW620 hlwb tom qab 48 teev (Daim duab 1D, p < 0.05 rau txhua tus). Tom qab 72 teev ntawm kev kho mob, cov nyhuv tib yam tau pom tsuas yog rau ob qhov siab tshaj plaws (p <0.05) thaum 0.25 thiab 0.5 mg / mL concentrations tsis pom muaj txiaj ntsig zoo piv rau kev tswj hwm (p> 0.05). Qhov cuam tshuam ntawm 0.5 thiab 1 mg / mL CTE kev kho mob ntawm qhov induction ntawm apoptosis tau kuaj ntxiv hauv plaub kab ntawm tes (Daim duab 2). Ib qho ntxiv ntawm cov hlwb hauv apoptosis thaum ntxov tau kuaj pom hauv HCT116 thiab LoVo tom qab 24 teev ntawm kev kho mob nrog 0.5 mg / mL (p<0.05, Figure 2B and 2C) and in all cell lines at 1 mg/mL (p<0.05). A significant increase in necrotic or late apoptotic cell number was further observed in CaCo2 and SW620 cell lines (p<0.05, Figure 2A and 2D).
Lub peev xwm ntawm CTE rau induce intracellular ROS ntau lawm yog pom nyob rau hauv daim duab 3. Peb teev tom qab kev kho CTE muaj ib tug muaj zog nce nyob rau hauv intracellular ROS ntau lawm nyob rau hauv tag nrho cov kab ntawm tes (p<0.05). The intracellular ROS production increased progressively throughout the 25 hours of treatment in a time and concentration-dependent manner. Furthermore, the staining of cells with a mitochondria-targeted probe revealed a strong impact of CTE on mitochondrial superoxide production in a concentration-dependent manner (Figure 4). The highest increase in superoxide production by mitochondria was observed in HCT116 (69%, Figure 4B) and LoVo cells (82%, Figure 4C) following 24 hours of treatment with 1 mg/mL of CTE.


Daim duab 1:
Cov txiaj ntsig ntawm Cistanche tubulosa ntawm kev muaj peev xwm ntawm cov kab mob qog noj ntshav ntawm txoj hnyuv. Cell viability ntsuas los ntawm MTT kev soj ntsuam ntawm (A) CaCo2, (B) HCT116, (C) LoVo, thiab (D) SW620 hlwb raug nthuav tawm raws li feem pua ntawm kev tswj tsis tau kho cov kab mob qog noj ntshav. Qhov tseem ceeb (± SD) rau 5 replicates ntawm tus neeg sawv cev sim tau muab: (*) qhov tseem ceeb p<0.05 in comparison to control untreated respective cells.

Daim duab 2:
Cistanche tubulosa dej extract induces apoptosis nyob rau hauv tib neeg txoj hnyuv kab mob hlwb. Annexin-V-FITC flow cytometry tsom xam ntawm (A) CaCo2, (B) HCT116, (C) LoVo, thiab (D) SW620 hlwb raug nthuav tawm raws li feem pua ntawm kev tswj tsis tau kho cov kab mob qog noj ntshav. Tus nqi nruab nrab (± SD) rau 3 qhov kev hloov pauv ntawm tus neeg sawv cev sim tau muab: (*) qhov tseem ceeb p<0.05 in comparison to control untreated respective cells.

Daim duab 3:
Cistanche tubulosa dej extract induces intracellular ROS ntau lawm nyob rau hauv ib lub sij hawm- thiab koob tshuaj-nyob ntawm seb. ROS ntau lawm ntsuas los ntawm DCFH-DA assay hauv (A) CaCo2, (B) HCT116, (C) LoVo, thiab (D) SW620 hlwb raug nthuav tawm raws li qhov txhais tau tias RFU qhov tseem ceeb (± SD) rau qhov sib npaug ntawm 5- ib tug sawv cev sim. (*) Qhov tseem ceeb p<0.05 in comparison to control untreated colon cancer cells.

Daim duab 4:
Cistanche tubulosa dej extract induces mitochondrial superoxide ntau lawm nyob rau hauv tib neeg txoj hnyuv kab mob hlwb. Fluorescence siv ntawm mitochondria-targeted MitoSOX Liab sojntsuam hauv A) CaCo2, (B) HCT116, (C) LoVo thiab (D) SW620 hlwb raug nthuav tawm raws li feem pua ntawm kev tswj tsis tau kho cov kab mob qog noj ntshav. Qhov tseem ceeb (± SD) rau 5 replicates ntawm tus neeg sawv cev sim tau muab: (*) qhov tseem ceeb p<0.05 in comparison to control untreated colon cancer cells.

Kev sib tham
Txawm hais tias cov kev tshawb fawb yav dhau los tau tshaj tawm ntau yam tshuaj ntawm Cistanche tubulosa, qhov no yog thawj daim ntawv tshaj tawm ntawm nws cov tshuaj tiv thaiv kab mob hauv cov hlwb malignant. Cistanche tubulosa bioactive tebchaw muab rho tawm nrog dej, ib tug heev polar solvent, pom muaj zog anticancer bioactivity. Peb tau yav tas los piv qhov ua tau zoo ntawm Cistanche tubulosa solubilized hauv dej tiv thaiv lwm cov kuab tshuaj xws li methanol thiab ethyl acetate, tab sis cov dej rho tawm tau nthuav tawm qhov kev cog lus zoo tshaj plaws los tiv thaiv kab mob (cov ntaub ntawv tsis qhia).
Peb tau pom lub peev xwm ntawm CTE ntawm 1 mg / mL thiab 2 mg / mL los inhibit 60 feem pua ntawm kev loj hlob ntawm ob qho tib si thawj thiab kab mob qog nqaij hlav qog noj ntshav, qhia txog lub luag haujlwm tseem ceeb ntawm Cistanche tubulosa raws li kev kho mob qog noj ntshav. Piv nrog rau cov hlwb ib txwm muaj, cov qog nqaij hlav cancer feem ntau tshwm sim los ntawm kev cuam tshuam hauv redox homeostasis thiab ib lub tswv yim zoo ntawm kev kho mob qog noj ntshav tam sim no yog ua kom cov cellular oxidative kev nyuaj siab (Yang et al, 2013). Txawm hais tias lub cev tsis muaj zog ntawm ROS muaj lub luag haujlwm tseem ceeb hauv kev taw qhia cov molecules, ntau ROS ntau lawm tuaj yeem ua rau mob qog noj ntshav thiab mob qog noj ntshav (Liou thiab Storz, 2010). Paradoxically, qhov tsis sib xws hauv cellular redox homeostasis ua rau cov qog nqaij hlav qog nqaij hlav ntau dua rau ROSinduced cell tuag (Jaganjac li al., 2008; Nogueira and Hay, 2013). Cov nyhuv antiproliferative ntawm CTE qhia nyob rau hauv txoj kev tshawb no tuaj yeem kho los ntawm ntau yam ntxiv- thiab intracellular mechanisms ntawm paub thiab tsis paub tebchaw nyob rau hauv extract, tsom ntau txoj hauv kev uas ua lub luag haujlwm tseem ceeb hauv apoptosis. Txhawm rau sib txawv ntawm ntau hom kev tuag ntawm tes, peb tau tshawb xyuas lub peev xwm txheej txheem ua lub luag haujlwm rau CTE-induced cytotoxicity
Peb cov ntaub ntawv qhia tias CTE nce intracellular ROS ntau lawm thiab yog li ROS-induced cell tuag. Lub Redox lub xeev ntawm lub cell kuj ua lub luag haujlwm tseem ceeb hauv kev tswj hwm apoptosis thiab mitochondrial electron thauj saw yog ib qho ntawm cov chaw loj ntawm cellular ROS tiam (Trachootham li al., 2008). Tsis tas li ntawd, lub intracellular ROS tuaj yeem ua rau cellular apoptosis ntawm ob qho tib si mitochondria-dependent thiab txoj kev ywj pheej (Sinha li al., 2013). Tseeb, peb cov ntaub ntawv tseem qhia tau hais tias CTE-induced phosphatidylserine externalization, yog ib qho tshwm sim hauv apoptosis, nyob rau hauv ob qho tib si thawj thiab metastatic kab mob qog noj ntshav, qhia tias cov txheej txheem ntawm CTE-vim tuag yog kho los ntawm apoptosis es tsis yog necrosis. Kev ua kom apoptosis hauv cov qog nqaij hlav cancer yog lub tswv yim kho thiab ntau cov tshuaj tiv thaiv kab mob tuaj yeem ua rau muaj kev cuam tshuam apoptotic hauv cov qog nqaij hlav cancer.
Cov khoom sib xyaw lossis cov khoom rho tawm nrog cov haujlwm pro-apoptotic hauv cov qog nqaij hlav cancer yog li ntawd muaj txiaj ntsig zoo hauv kev tshawb fawb tshuaj tiv thaiv kab mob (Wong, 2011). Txhawm rau txiav txim siab seb CTE-induced pro-apoptotic effect yog kho los ntawm mitochondria-induced ROS mechanism, peb ntsuas superoxide ntau lawm siv mitochondria-targeted fluorescent sojntsuam hauv CTE-kho hlwb. Peb cov ntaub ntawv qhia meej meej tias CTE txhawb nqa mitochondrial superoxide ntau lawm qhia tias Cistanche tubulosa anticancer kev ua haujlwm tsawg kawg hauv ib feem kev kho los ntawm mitochondria-induced ROS mechanism.
Cov lus xaus
Hauv kev xaus, peb cov ntaub ntawv qhia tias cov dej rho tawm ntawm cov nroj tsuag suab puam Cistanche tubulosa tuaj yeem sawv cev rau tus neeg sib tw muaj txiaj ntsig rau kev tiv thaiv kab mob ua ke nrog rau lwm cov kev kho mob rau kev tiv thaiv thiab kho mob qog noj ntshav. Peb kuj qhia tau hais tias cov tshuaj toxicity ntawm cov nroj tsuag extract tiv thaiv cov qog nqaij hlav cancer yog kho los ntawm kev nce intracellular ROS ntau lawm thiab, tsawg kawg yog ib feem, los ntawm mitochondrial-dependent apoptosis. Cov kev tshawb fawb ntxiv tau txuas ntxiv mus rau kev cais tawm thiab ua tus yam ntxwv ntawm tus kheej cov neeg ua haujlwm lom neeg muaj lub luag haujlwm rau kev ua haujlwm tiv thaiv kabmob.
Kev tshawb fawb ntxiv yog xav tau los ntsuas qhov muaj peev xwm siv cov extract no ua tus neeg sawv cev zoo chemopreventive thiab nkag siab txog cov txheej txheem ntawm kev ua ntawm cov qog nqaij hlav hauv plab ntawm qib molecular. Ntxiv rau kev tshawb fawb txog kev kho mob thiab kev kho mob ntxiv kuj tseem xav tau kom paub meej txog cov txiaj ntsig kev noj qab haus huv ntawm Cistanche tubulosa rau kev tiv thaiv qog noj ntshav.

TXOJ CAI
Kev txhawb nqa nyiaj txiag thiab kev txhawb nqa: Txoj kev tshawb no tau txhawb nqa los ntawm Anti-Doping Lab Qatar.
Kev tsis sib haum xeeb ntawm kev txaus siab: Cov neeg sau ntawv tshaj tawm tsis muaj teeb meem ntawm kev txaus siab.
REFERENCES
Balunas MJ, Kinghorn, AD. Tshuaj nrhiav tau los ntawm cov nroj tsuag tshuaj. Lub neej Sci. 2005; 78:431-41.
Brenner H, Kloor M, Pox CP. mob qog nqaij hlav hauv plab. Lancet 2014; 383, 1490-502.
Cindric M, Cipak A, Zapletal E, Jaganjac M, Milkovic L, Waeg G, Stolc S, Zarkovic N, Suzana Borovic S. Stobadine attenuates kev puas tsuaj ntawm cov kab mob hauv plab hnyuv uas tshwm sim los ntawm 4-hydroxynonenal. Toxicol In Vitro. 2013; 27:426-32.
Cragg GM, Newman DJ. Nroj tsuag ua ib qhov chaw ntawm cov tshuaj tiv thaiv kab mob.JEthnopharmacol. 2005; 100:72-9.
da Rocha AB, Lopes RM, Schwartsmann G. Ntuj cov khoom hauv kev kho mob qog noj ntshav. CurrOpinPharmacol. 2001; 1:364-9. Jaganjac M, Matijevic T, Cindric M, Cipak A, Mrakovcic L, Gubisch W, Zarkovic N. Induction ntawm CMV-1 txhawb nqa los ntawm 4-hydroxy-2- nominal nyob rau hauv tib neeg embryonic lub raum hlwb. Acta Biochim Pol. 2010; 57:179-83.
Jaganjac M, Poljak-Blazi M, Zarkovic K, Schaur RJ, Zarkovic N. Kev koom tes ntawm granulocytes hauv spontaneous regression ntawm Walker 256 carcinoma. Cancer Lett. Xyoo 2008; 260:180-6
Jiang Y, Tu PF. Kev soj ntsuam ntawm cov tshuaj lom neeg hauv Cistanche hom. J Chromatogr A. 2009; 1216:1970-9.
Liou GY, Storz P. Reactive oxygen hom kab mob qog noj ntshav. Dawb Radic Res. 2010; 44:479-96.
Morikawa T, Pan Y, Ninomiya K, Imura K, Matsuda H, Yoshikawa M, Yuan D, Muraoka O. Acylated phenylethanoid aminoglycosides nrog hepatoprotective kev ua los ntawm cov suab puam cog Cistanche tubulosa. Bioorg Med Chem. 2010; 18:1882-90.
Nogueira V, Hay N. Molecular pathways: reactive oxygen species homeostasis in cancer cells and implications for cancer therapy. Clin Cancer Res. 2013; 19:4309-14.
Poljak-Blazi M, Jaganjac M, Sabol I, Mihaljevic B, Matovina M, Grce M. Cov nyhuv ntawm ferric ions ntawm reactive oxygen hom tsim, ncauj tsev menyuam kab mob qog noj ntshav thiab E6/E7 oncogene qhia. Toxicol Vitro. 2011; 25:160-6.
Saibu GM, Katerere DR, Rees DJG, Meyer M. In vitro cytotoxic thiab pro-apoptotic teebmeem ntawm cov dej rho tawm ntawm Tulbaghia violacea nplooj thiab qhov muag teev. J Ethnopharmacol. 2015; 164:203-9.
Sinha K, Das J, Pal PB, Sil PC. Oxidative stress: mitochondria-dependent thiab mitochondria-kev ywj pheej txoj kev ntawm apoptosis. Arch Toxicol.2013; 87:4 :ua. Trachootham D, Lu W, Ogasawara MA, Nilsa RD, Huang P. Redox regulation of cell survival. Antioxidant Redox teeb liab. 2008; 10:1343- 74.
Weidner C, Rousseau M, Plauth A, Wowro SJ, Fischer C, Abdel-Aziz H, Sauer S. Melissa officinalis extract induces apoptosis thiab inhibits proliferation hauv cov qog nqaij hlav hauv plab los ntawm kev tsim cov pa oxygen reactive hom. Phytomedicine. 2015; 22:262-70.
Wong RS. Apoptosis hauv qog noj ntshav: los ntawm pathogenesis mus rau kev kho mob. J ExpClin Cancer Res. Xyoo 2011; 30:87.
Wu SH, Chou FP, Chyau CC, Chen JH, Tu SF, Lin HH. Anti-cancerous teebmeem ntawm Wasabia japonica extract nyob rau hauv Hep3B daim siab mob hlwb hlwb ntawm ROS tsub zuj zuj, DNA puas, thiab p73- kho apoptosis. J Funct Foods. 2015; 14:445-55.
Xiong WT, Gu L, Wang C, Sun HX, Liu X. Antihyperglycemic thiab hypolipidemic teebmeem ntawm Cistanche tubulosa hauv hom 2 mob ntshav qab zib mellitus db/db nas. J Ethnopharmacol. 2013; 150:935-45.
Xu R, Sun S, Zhu W, Xu C, Liu Y, Shen L, Shi Y, Chen J. Ntau kauj ruam infrared macro-ntiv tes nta ntawm ethanol rho tawm los ntawm ntau hom Cistanche hauv Suav teb ua ke nrog HPLC ntiv tes. J Mol Struct. 2014; 1069:236-244.
Yang Y, Karakhanova S, Werner J, Bazhin AV. Reactive oxygen hom nyob rau hauv mob cancer biology thiab anticancer kho. Curr Med Chem. 2013; 20:3677-92.
Yoshikawa M, Matsuda H, Morikawa T, Xie H, Nakamura S, Muraoka O. Phenylethanoid aminoglycosides thiab acylated oligo qab zib nrog vasorelaxant kev ua los ntawm Cistanche tubulosa. Bioorg Med Chem. 2006; 14:7468-75.
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