Gayathri Ramachandran, Gunadharini Dharmalingam Nandagopal, Arunkumar Arumugam, Senthilkumar Kalimuthu, Krishnamoorthy Gunasekar, Banudevi Sivanantham, Vignesh Ramamoorthy Chandrakanth, Arunakaran Jagadeesan
Department of Endocrinology, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai, Tamil Nadu 600 113, India.
Mol Cell Biochem. 2009 Jan;320(1-2):197-203. doi: 10.1007/s11010-008-9903-5. Epub 2008 Aug 31.
Prostate cancer is a leading cause of death among the aging men. Surgical or radiotherapy is effective when the cancer is confined to the prostate gland but once the cancer spreads beyond the pelvis even chemotherapy and hormonal ablation therapy fails in curing this disease. Our previous studies have shown that diallyl disulfide (DADS) induces cell cycle arrest and also induces apoptosis in PC-3 cells. And now the present study is focused to see whether there is an activation of caspase cascade pathway. Hence, in the present study the apoptotic effect of DADS is studied by Western blot analysis of caspase-3, -9, -10 and Bcl-2, Bad, and Bax protein. The Apoptotic cells were assessed by Hoechst 33342 staining with 25 and 40 microM concentrations of DADS for 24 h. The results have shown that DADS at 25 and 40 microM concentrations has induced the activation of caspases. There is a significant increase in the expression of caspases (3, 9, and 10). The proapoptotic protein Bax has significantly increased at 40 microM of DADS treatment and there is significant increase of Bad protein at both the concentration. Bcl-2 protein has significantly decreased in DADS treated cells. Therefore, the present investigation serves as evidence that DADS may be a therapeutic drug in the treatment of prostate cancer.
前列腺癌是老年男性主要的死亡原因之一。当癌症局限于前列腺时，手术或放疗是有效的，但一旦癌症扩散到骨盆以外，即使化疗和激素消融治疗也无法治愈这种疾病。我们之前的研究表明，二烯丙基二硫化物（DADS）可诱导细胞周期停滞，并诱导PC-3细胞凋亡。现在本研究着重观察是否存在半胱天冬酶级联途径的激活。因此，在本研究中，通过对caspase-3、-9、-10以及Bcl-2、Bad和Bax蛋白进行蛋白质印迹分析，研究了DADS的凋亡作用。用25和40微摩尔浓度的DADS处理细胞24小时，通过Hoechst 33342染色评估凋亡细胞。结果表明，25和40微摩尔浓度的DADS可诱导半胱天冬酶的激活。半胱天冬酶（3、9和10）的表达显著增加。在40微摩尔DADS处理时，促凋亡蛋白Bax显著增加，且在两个浓度下Bad蛋白均显著增加。在DADS处理的细胞中，Bcl-2蛋白显著减少。因此，本研究证明DADS可能是一种治疗前列腺癌的药物。
