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.