It has been shown earlier that
plumbagin, a naturally occurring naphthaquinone has specific anticancer activity in BRCA1 blocked
ovarian cancer cells.
Plumbagin can induce
estrogen dependent cell signaling and apoptosis in BRCA1 blocked
ovarian cancer cells. Being a
reactive oxygen species (ROS) generator and apoptosis inducing agent,
plumbagin has immense potential as a promising
anticancer agent. In this study we analyzed whether there would be increased anticancer activity if the positions of the functional groups on
plumbagin were altered and further to analyze the detailed molecular mechanism of action of the lead molecule. Methods like MTT assay, apoptosis analysis by flow cytometry, assessment of mitochondrial membrane potential-Δψm , suppression subtractive hybridization, microarray, molecular docking and
estrogen receptor-
DNA binding activity by electrophoresis mobility shift assay (EMSA) were adopted for assessing the anticancer activity. Consequently we found that,
plumbagin was the most potent
anticancer agent when compared to structurally related compounds. The anti-
cancer activities were in the order
plumbagin > 1,4-naphthaquinone >
juglone >
lawsone >
menadione. Molecular docking studies showed that
plumbagin could be well docked in the receptor
ligand complex of TRAIL-DR5 complexes to activate the extrinsic pathway of apoptosis. Since the antiproliferative activity of
plumbagin could be reduced by inhibiting ERα, we speculated that
plumbagin interferes with the binding of ERα to ERE and we confirmed this by EMSA. This study clearly indicates that
plumbagin can induce multiple pathways of apoptosis and cell cycle arrest in BRCA1 blocked cells compared to unblocked cells.