路易斯安那州紐奧良市杜蘭大學(xué)醫(yī)學(xué)院的研究人員證明Thymoquinone (TQ),，一種來自黑種草油(Nigella sativa) 的主要成份,，可以抑制一些高度惡化的前列腺癌(PCa)細(xì)胞株在試管內(nèi)的生長。雖然之前已有報導(dǎo)TQ在不同的癌細(xì)胞株有抑制生長的作用,，但它的分子機(jī)制尚不清楚。TQ因為在構(gòu)造上類似粒腺體輔酶-Q (co-Q)復(fù)合物的普醌，所以探討它如何影響氧自由基的制造,。
他們發(fā)現(xiàn)TQ在20 - 100 M 濃度下會在LNCaP及C4-2B細(xì)胞株產(chǎn)生大量的反應(yīng)性氧分子(ROS)，細(xì)胞內(nèi)的小分子抗氧化物谷胱甘肽(GSH)量也會跟著降低,，這和TQ造成的抗癌作用有關(guān),，可以用外加GSH類似物 N-乙醯半胱氨酸(NAC)而抑制。氧自由基通常是作為腫瘤細(xì)胞增殖訊號的第二信息分子,，細(xì)胞內(nèi)ROS的產(chǎn)生和它被抗氧化物去活化間有一個重要的平衡,，會決定細(xì)胞是生長或凋亡。他們發(fā)現(xiàn)TQ處理的PCa細(xì)胞株有一些誘導(dǎo)細(xì)胞凋亡的分子如GAD45,、AIF-1會顯著地增加,，這研究結(jié)果將刊登在2010年六月份《實驗生物及醫(yī)學(xué)》(Experimental Biology and Medicine)期刊上。
Mondal博士說明＂互補(bǔ)與另類醫(yī)學(xué)(CAM) 在癌癥病人的附屬治療上愈來愈重要,，不僅可以減輕化學(xué)治療的副作用,，也可以增加抗癌的效果，天然物質(zhì)的低副作用性質(zhì)在運用它們作為抗癌的附屬療法時也是一個重要的因素,，我們之前的研究(Exp Biol Med; 2009,234(4): 442-53),，已發(fā)現(xiàn)很低濃度的TQ 在胰臟??-細(xì)胞可以減少ROS的制造，增加GSH的量,，因而恢復(fù)抗HIV藥物Nelfinavir對這些細(xì)胞造成的不良副作用?，F(xiàn)在這個研究發(fā)現(xiàn)高濃度的TQ (> 20 M)所產(chǎn)生的ROS可能對研發(fā)抗癌的治療帶來新看法，尤其是對荷爾蒙失效,，很難治療的前列腺癌病人,。
這研究團(tuán)隊由Krishna C. Agrawal博士(已過世)領(lǐng)導(dǎo)，包括Sandeep Koka博士,，以前是Agrawal博士指導(dǎo)的研究生,、以及杜蘭大學(xué)的二位教授 Asim B. Abdel-Mageed博士和Debasis Mondal博士,，他們成功地驗證TQ能抑制前列腺癌細(xì)胞株的生長是因為TQ能誘導(dǎo)氧化壓力造成的假說，因為黑種草油在中東國家已使用好幾百年,，他們建議TQ這活性物質(zhì)或油本身,，可以單獨使用，或做為化學(xué)治療的附屬療法,，用來治療高度惡化的前列腺癌,。
實驗生物及醫(yī)學(xué)期刊主編Steven R. Goodman說：“Koka等人發(fā)現(xiàn)Thymoquinone可以有效地殺死荷爾蒙依賴性及非依賴性的前列腺癌細(xì)胞株，它作用機(jī)制是誘發(fā)氧化壓力而抑制GSH的量,，這表示在高度惡化的前列腺癌細(xì)胞,，氧化壓力可以降低癌細(xì)胞的生長，增加癌細(xì)胞的凋亡,。”（生物谷Bioon.com）
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生物谷推薦原文出處：
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.
