Maiuthed Arnatchai, Pinkhien Tatchakorn, Chamni Supakarn, Suwanborirux Khanit, Saito Naoki, Petpiroon Nareerat, Chanvorachote Pithi
Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.
Cell-Based Drug and Health Product Development Research Unit, Chulalongkorn University, Bangkok, Thailand.
Anticancer Res. 2017 Nov;37(11):6259-6267. doi: 10.21873/anticanres.12077.
A newly-synthesized derivative of renieramycin M (RM), an anticancer lead compound isolated from the blue sponge Xestospongia sp., hydroquinone 5-O-cinnamoyl ester (CIN-RM), was investigated here for its activity against non-small cell lung cancer cells.
Cytotoxicity effects of CIN-RM and RM on H292 lung cancer cells were determined by the MTT assay. We also investigated the mechanism of CIN-RM-mediated apoptosis and mechanism of action of this compound by western blotting.
CIN-RM showed more potent cytotoxicity than its parental compound (RM) against H292 lung cancer cells. At concentrations of 15-60 μM, CIN-RM significantly induced apoptosis by increasing expression of apoptosis-inducing factor (AIF) and activation of caspase-3 and -9. For up-stream mechanism, CIN-RM mediated apoptosis through a p53-dependent mechanism, that consequently down-regulated anti-apoptotic B-cell lymphoma 2 (BCL2), while increasing the level of pro-apoptotic BCL2-associated X (BAX). In addition, phosphorylation of pro-survival protein AKT was found to be dramatically reduced.
This study revealed the potential of CIN-RM for apoptosis induction and in the development of a novel anticancer agent.
从蓝色海绵Xestospongia sp.中分离出的抗癌先导化合物雷尼霉素M（RM）的一种新合成衍生物对苯二酚5 - O - 肉桂酸酯（CIN - RM），在此研究其对非小细胞肺癌细胞的活性。
通过MTT法测定CIN - RM和RM对H292肺癌细胞的细胞毒性作用。我们还通过蛋白质印迹法研究了CIN - RM介导的细胞凋亡机制和该化合物的作用机制。
CIN - RM对H292肺癌细胞显示出比其母体化合物（RM）更强的细胞毒性。在15 - 60 μM浓度下，CIN - RM通过增加凋亡诱导因子（AIF）的表达以及激活半胱天冬酶 - 3和 - 9显著诱导细胞凋亡。对于上游机制，CIN - RM通过p53依赖性机制介导细胞凋亡，从而下调抗凋亡的B细胞淋巴瘤2（BCL2），同时增加促凋亡的BCL2相关X蛋白（BAX）的水平。此外，发现促生存蛋白AKT的磷酸化显著降低。
本研究揭示了CIN - RM在诱导细胞凋亡和开发新型抗癌药物方面的潜力。
