细胞凋亡
前列腺癌
去极化
线粒体
雄激素
膜电位
细胞生物学
癌症研究
生物
化学
癌症
内分泌学
生物物理学
生物化学
激素
遗传学
作者
Kausik Bishayee,Debrup Chakraborty,Samrat Ghosh,Naoual Boujedaini,Anisur Rahman Khuda‐Bukhsh
标识
DOI:10.1016/j.ejphar.2012.10.041
摘要
When the prostate cancer cells become unresponsive to androgen therapy, resistance to chemotherapy becomes imminent, resulting in high mortality. To combat this situation, lycopodine, a pharmacologically important bioactive component derived from Lycopodium clavatum spores, was tested against hormone sensitive (LnCaP) and refractory (PC3) prostate cancer cells in vitro. This study aims to check if lycopodine has demonstrable anti-cancer effects and if it has, to find out the possible mechanism of its action. The MTT assay was performed to evaluate the cytotoxic effect. Depolarization of mitochondrial membrane potential, cell cycle, EGF receptor activity and apoptosis were recorded by FACS; profiles of different anti- and pro-apoptotic genes and their products were studied by semi-quantitative RT-PCR, indirect-ELISA, western blotting. Drug–DNA interaction was determined by CD spectroscopy. Administration of lycopodine down-regulated the expression of 5-lipoxygenase and the 5-oxo-ETE receptor (OXE receptor1) and EGF receptor, and caused up-regulation of cytochrome c with depolarization of mitochondrial inner membrane potential, without palpable change in p53 activity, resulting in apoptosis, cell arrest at G0/G1 stage and ultimately reduced proliferation of cancer cells; concomitantly, there was externalization of phosphotidyl serine residues. CD spectroscopic analysis revealed intercalating property of lycopodine with DNA molecule, implicating its ability to block cellular DNA synthesis. The overall results suggest that lycopodine is a promising candidate suitable for therapeutic use as an anti-cancer drug.
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