生物谷：來自南加州醫(yī)科大學(xué)的科學(xué)家最近發(fā)現(xiàn),，大蒜可以殺死造成膠質(zhì)母細(xì)胞瘤（glioblastoma）的細(xì)胞，膠質(zhì)母細(xì)胞瘤是一種致命的腦部癌癥,。
南加州大學(xué)醫(yī)科大學(xué)神經(jīng)科學(xué)教授Swapan Ray和Narendra Banik表示，他們在研究如何在不損傷健康細(xì)胞的同時(shí)殺死癌細(xì)胞的過程中取得了這一發(fā)現(xiàn)，當(dāng)?shù)貓?bào)紙報(bào)道了這一研究成果,。
Banik表示：“當(dāng)疾病發(fā)生時(shí)，人們希望殺死腫瘤細(xì)胞,，而同時(shí)又保護(hù)其它健康細(xì)胞,。我們的研究就是要觀察這些物質(zhì)究竟有多大的作用。”
Banik,，Ray和博士后Arabinda Das針對癌細(xì)胞測試了多種有機(jī)化合物的效果,。他們特地在研究中測試了大蒜物質(zhì)，因?yàn)榇笏庖恢币該碛兄委熂膊〉墓πФ劽?。結(jié)果Ray表示,，他們測試的三種有機(jī)硫化物能有效的阻止癌細(xì)胞的生長。
Ray說：“我們的研究證明了從植物中提取的天然化合物可能將有效的控制人類腦部惡性腫瘤細(xì)胞的生長,。”Ray同時(shí)表示,，在針對人類病人的臨床性治療之前，還需要進(jìn)行更多的動物實(shí)驗(yàn),。
以上研究結(jié)果將發(fā)表在9月出版的美國癌癥學(xué)會刊物《癌癥》（Cancer）上,。 （援引教育部科技發(fā)展中心）
原文鏈接：http://www.physorg.com/news107624547.html
原始出處:
Cancer
Volume 110, Issue 5 , Pages 1083 - 1095
Published Online: 23 Jul 2007
Garlic compounds generate reactive oxygen species leading to activation of stress kinases and cysteine proteases for apoptosis in human glioblastoma T98G and U87MG cells
Arabinda Das, PhD, Naren L. Banik, PhD, Swapan K. Ray, PhD *
Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina
email: Swapan K. Ray ([email protected])
*Correspondence to Swapan K. Ray, Department of Neurosciences, Medical University of South Carolina, 96 Jonathan Lucas Street, Suite 325E, Charleston, SC 29425
Fax: (843) 792-8626
Funded by:
National Cancer Institute; Grant Number: CA-91460
NINDS; Grant Number: NS-57811
Keywords
apoptosis ?diallyl sulfide ?diallyl disulfide ?diallyl trisulfide ?glioblastoma ?oxidative stress
Abstract
BACKGROUND.
Garlic-derived organosulfur compounds such as diallyl sulfide (DAS), diallyl disulfide (DADS), and diallyl trisulfide (DATS) provide significant protection against carcinogenesis.
METHODS.
Dose-dependent cytotoxic effects of the garlic compounds (DAS, DADS, and DATS) were tested in human glioblastoma T98G and U87MG cells. Wright staining and ApopTag assay confirmed induction of apoptosis. Measurements showed that production of reactive oxygen species (ROS) and an increase in intracellular free [Ca2+] promoted apoptosis. Western blot analysis indicated that increased expression and activities of the stress kinases and cysteine proteases caused apoptosis. Use of JC-1 showed changes in mitochondrial membrane potential (m) for mediation of apoptosis. Use of the specific inhibitors monitored the activation of different kinases and proteases in apoptosis.
RESULTS.
Treatment of glioblastoma cells with garlic compounds triggered production of ROS that induced apoptosis with the phosphorylation of p38 MAPK and activation of the redox-sensitive JNK1 pathway. Pretreatment of cells with ascorbic acid attenuated ROS production, p38 MAPK phosphorylation, and JNK1 activation. Pretreatment with JNK1 inhibitor I also significantly reduced cell death. Increases in intracellular free [Ca2+], expression of calreticulin, and activation of caspase-4 indicated involvement of endoplasmic reticulum (ER) stress in apoptosis. Other events in apoptosis included overexpression of Bax, down-regulation of Bcl-2 and some BIRC proteins, mitochondrial release of cytochrome c and Smac into the cytosol, and activation of calpain, caspase-9, and caspase-3.
CONCLUSIONS.
Garlic compounds induced apoptosis in glioblastoma cells due toproduction of ROS, increase in ER stress, decrease in m, and activation of stress kinases and cysteine proteases. Cancer 2007. © 2007 American Cancer Society.
