生物谷：来自南加州医科大学的科学家最近发现，大蒜可以杀死造成胶质母细胞瘤（glioblastoma）的细胞，胶质母细胞瘤是一种致命的脑部癌症。
南加州大学医科大学神经科学教授Swapan Ray和Narendra Banik表示，他们在研究如何在不损伤健康细胞的同时杀死癌细胞的过程中取得了这一发现，当地报纸报道了这一研究成果。
Banik表示：“当疾病发生时，人们希望杀死肿瘤细胞，而同时又保护其它健康细胞。我们的研究就是要观察这些物质究竟有多大的作用。”
Banik，Ray和博士后Arabinda Das针对癌细胞测试了多种有机化合物的效果。他们特地在研究中测试了大蒜物质，因为大蒜一直以拥有治疗疾病的功效而闻名。结果Ray表示，他们测试的三种有机硫化物能有效的阻止癌细胞的生长。
Ray说：“我们的研究证明了从植物中提取的天然化合物可能将有效的控制人类脑部恶性肿瘤细胞的生长。”Ray同时表示，在针对人类病人的临床性治疗之前，还需要进行更多的动物实验。
以上研究结果将发表在9月出版的美国癌症学会刊物《癌症》（Cancer）上。 （援引教育部科技发展中心）
原文链接：http://www.physorg.com/news107624547.html
原始出处:
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 (raysk@musc.edu)
*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.
