Ramamoorthy Manjula Devi, Kumar Ashok, Ayyavu Mahesh, Dhiraviam Kannan Narayanan
Department of Plant Biotechnology, School of Biotechnology, Madurai Kamaraj University, Madurai-625021, Tamilnadu, India.
School of Biological Sciences, Madurai Kamaraj University, Madurai-625021, Tamilnadu, India.
Anticancer Agents Med Chem. 2018;18(9):1313-1322. doi: 10.2174/1871520618666180209152215.
Reserpine, an indole alkaloid commonly used for hypertension, is found in the roots of Rauwolfia serpentina. Although the root extract has been used for the treatment of cancer, the molecular mechanism of its anti-cancer activity on hormonal independent prostate cancer remains elusive.
we evaluated the cytotoxicity of reserpine and other indole alkaloids, yohimbine and ajmaline on Prostate Cancer cells (PC3) using MTT assay. We investigated the mechanism of apoptosis using a combination of techniques including acridine orange/ethidium bromide staining, high content imaging of Annexin V-FITC staining, flow cytometric quantification of the mitochondrial membrane potential and Reactive Oxygen Species (ROS) and cell cycle analysis.
Our results indicate that reserpine inhibits DNA synthesis by arresting the cells at the G2 phase and showed all standard sequential features of apoptosis including, destabilization of mitochondrial membrane potential, reduced production of reactive oxygen species and DNA ladder formation. Our in silico analysis further confirmed that indeed reserpine docks to the catalytic cleft of anti-apoptotic proteins substantiating our results.
Collectively, our findings suggest that reserpine can be a novel therapeutic agent for the treatment of androgen-independent prostate cancer.
利血平是一种常用于治疗高血压的吲哚生物碱，存在于蛇根木的根部。尽管根提取物已被用于治疗癌症，但其对激素非依赖性前列腺癌的抗癌活性分子机制仍不清楚。
我们使用MTT法评估了利血平和其他吲哚生物碱（育亨宾和阿马林）对前列腺癌细胞（PC3）的细胞毒性。我们结合吖啶橙/溴化乙锭染色、膜联蛋白V-FITC染色的高内涵成像、线粒体膜电位和活性氧（ROS）的流式细胞术定量以及细胞周期分析等技术，研究了细胞凋亡的机制。
我们的结果表明，利血平通过将细胞阻滞在G2期来抑制DNA合成，并显示出凋亡的所有标准序列特征，包括线粒体膜电位不稳定、活性氧产生减少和DNA梯带形成。我们的计算机分析进一步证实，利血平确实与抗凋亡蛋白的催化裂隙结合，证实了我们的结果。
总体而言，我们的研究结果表明，利血平可能是一种治疗雄激素非依赖性前列腺癌的新型治疗药物。
