路易斯安那州纽奥良市杜兰大学医学院的研究人员证明Thymoquinone (TQ)，一种来自黑种草油(Nigella sativa) 的主要成份，可以抑制一些高度恶化的前列腺癌(PCa)细胞株在试管内的生长。虽然之前已有报导TQ在不同的癌细胞株有抑制生长的作用，但它的分子机制尚不清楚。TQ因为在构造上类似粒腺体辅酶-Q (co-Q)复合物的普醌，所以探讨它如何影响氧自由基的制造。
他们发现TQ在20 - 100 M 浓度下会在LNCaP及C4-2B细胞株产生大量的反应性氧分子(ROS)，细胞内的小分子抗氧化物谷胱甘肽(GSH)量也会跟着降低，这和TQ造成的抗癌作用有关，可以用外加GSH类似物 N-乙醯半胱氨酸(NAC)而抑制。氧自由基通常是作为肿瘤细胞增殖讯号的第二信息分子，细胞内ROS的产生和它被抗氧化物去活化间有一个重要的平衡，会决定细胞是生长或凋亡。他们发现TQ处理的PCa细胞株有一些诱导细胞凋亡的分子如GAD45、AIF-1会显着地增加，这研究结果将刊登在2010年六月份《实验生物及医学》(Experimental Biology and Medicine)期刊上。
Mondal博士说明＂互补与另类医学(CAM) 在癌症病人的附属治疗上愈来愈重要，不仅可以减轻化学治疗的副作用，也可以增加抗癌的效果，天然物质的低副作用性质在运用它们作为抗癌的附属疗法时也是一个重要的因素，我们之前的研究(Exp Biol Med; 2009,234(4): 442-53)，已发现很低浓度的TQ 在胰脏??-细胞可以减少ROS的制造，增加GSH的量，因而恢复抗HIV药物Nelfinavir对这些细胞造成的不良副作用。现在这个研究发现高浓度的TQ (> 20 M)所产生的ROS可能对研发抗癌的治疗带来新看法，尤其是对荷尔蒙失效，很难治疗的前列腺癌病人。
这研究团队由Krishna C. Agrawal博士(已过世)领导，包括Sandeep Koka博士，以前是Agrawal博士指导的研究生、以及杜兰大学的二位教授 Asim B. Abdel-Mageed博士和Debasis Mondal博士，他们成功地验证TQ能抑制前列腺癌细胞株的生长是因为TQ能诱导氧化压力造成的假说，因为黑种草油在中东国家已使用好几百年，他们建议TQ这活性物质或油本身，可以单独使用，或做为化学治疗的附属疗法，用来治疗高度恶化的前列腺癌。
实验生物及医学期刊主编Steven R. Goodman说：“Koka等人发现Thymoquinone可以有效地杀死荷尔蒙依赖性及非依赖性的前列腺癌细胞株，它作用机制是诱发氧化压力而抑制GSH的量，这表示在高度恶化的前列腺癌细胞，氧化压力可以降低癌细胞的生长，增加癌细胞的凋亡。”（生物谷Bioon.com）
最新癌症研究动态
NSMB：胰腺癌细胞变化机理
PLoS ONE：母乳Hamlet物质可杀死40种癌细胞
Nature：新合成抗体抑制癌细胞生长和血管生成
JBC：部分癌细胞存在命门 抗癌药物可长驱直入
生物谷推荐原文出处：
Exp. Biol. Med. 2010;235:751-760 doi:10.1258/ebm.2010.009369
Studies on molecular mechanisms of growth inhibitory effects of thymoquinone against prostate cancer cells: role of reactive oxygen species
Padma Sandeep Koka1, Debasis Mondal1, Michelle Schultz1, Asim B Abdel-Mageed2 and Krishna C Agrawal1,
1 Department of Pharmacology
2 Department of Urology, Tulane University School of Medicine, New Orleans, LA 70112, USA
Thymoquinone (TQ), an active ingredient of black seed oil (Nigella Sativa), has been shown to possess antineoplastic activity against a variety of experimental tumors. However, the precise mechanism of action of TQ is not known. We investigated the mechanism of action of TQ in androgen receptor (AR)-independent (C4-2B) and AR na??ve (PC-3) prostate cancer cells, as models of aggressive prostate cancers. Exposure (24–48 h) to TQ (25–150 ??mol/L) inhibited the growth of both C4-2B and PC-3 cells, with IC50 values of approximately 50 and 80 ??mol/L, respectively. Within one hour, TQ increased reactive oxygen species (ROS) levels (3-fold) and decreased glutathione (GSH) levels (60%) in both cell types. Pretreatment with N-acetylcysteine (NAC) inhibited both TQ-induced ROS generation and growth inhibition. TQ did not increase the activity of caspases and the caspase inhibitor, z-VAD-FMK did not decrease TQ-induced apoptosis. Furthermore, although TQ treatment resulted in the activation of Jun kinase (JNK), pretreatment with the JNK inhibitor, SP600125, did not protect cells from TQ. However, TQ significantly up-regulated the expressions of growth arrest and DNA damage inducible gene (GADD45{alpha}) and apoptosis-inducing factor-1 and down-regulated the expressions of several Bc12-related proteins, such as BAG-1, Bcl2, Bcl2A1, Bcl2L1 and BID. In C4-2B cells, TQ dose dependently inhibited both total and nuclear AR levels (4–5 fold) and AR-directed transcriptional activity (10–12 fold). Interestingly, this suppressive effect on AR was not prevented by NAC, which clearly suggested that TQ-induced cytotoxicity is not due to changes in AR regulation. These data suggest that TQ-induced cell death is primarily due to increased ROS generation and decreased GSH levels, and is independent of AR activity.