Plumbagin, a
naphthoquinone derived from the medicinal plant Plumbago zeylanica has been shown to exert anticancer and anti-proliferative activities in cells in culture as well as animal
tumor models. In our previous paper, we have reported the cytotoxic action of
plumbagin in plasmid pBR322
DNA as well as human peripheral blood lymphocytes through a redox mechanism involving
copper.
Copper has been shown to be capable of mediating the action of several
plant-derived compounds through production of
reactive oxygen species (ROS). The objective of the present study was to determine whether
plumbagin induces apoptosis in human
cancer cells through the same mechanism which we proposed earlier. Using
3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner
salt assay, 3-(4,5-B-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
bromide assay for cell growth inhibition,
histone/
DNA ELISA, homogeneous
caspase-3/7 assay for apoptosis as well as alkaline comet assay for
DNA single-strand breaks detection in this report, we confirm that
plumbagin causes effective cell growth inhibition, induces apoptosis and generates single-strand breaks in
cancer cells. Incubation of
cancer cells with scavengers of ROS and
neocuproine inhibited the cytotoxic action of
plumbagin proving that generation of ROS and Cu(I) are the critical mediators in
plumbagin-induced cell growth inhibition. This study is the first to investigate the
copper-mediated anticancer mechanism of
plumbagin in human
cancer cells and these properties of
plumbagin could be further explored for the development of
anticancer agents with higher therapeutic indices, especially for
skin cancer.