Many of the best-selling anticancer drugs are plant-derived. We tested for the anticancer properties of extracts isolated from Centaurea ainetensis, a plant species endemic to Lebanon and which is often used in
folk medicine. We performed bioassay-guided fractionation of Centaurea ainetensis extracts using a panel of normal and neoplastic murine cells to identify a component that is associated with antitumor activities. Among several compounds that were fractionated, the
sesquiterpene lactone,
Salograviolide A, was identified and found to exert the most significant growth inhibitory effects on neoplastic cells. At concentrations that were non-cytotoxic to primary keratinocytes, Centaurea ainetensis
crude extract and
Salograviolide A preferentially inhibited the proliferation of
papilloma and
squamous cell carcinoma (SCC) cell lines without significantly affecting the growth of normal cells. Flow cytometric analysis of
DNA content indicated that the inhibition of cell proliferation by Centaurea ainetensis
crude extract and
Salograviolide A was due to G0/G1 cell cycle arrest and increased pre-G0/G1, respectively. The increase in pre-G0/G1, and presumably apoptosis induction, in
Salograviolide A-treated keratinocytes was confirmed by
DNA Hoechst staining. Western blot analysis and electrophoretic mobility shift assay showed that both the
crude extract and the isolated molecule differentially modulated key cell cycle and apoptotic regulators as well as
NF-kappaB signaling.
Salograviolide A-induced growth inhibition in neoplastic cells was mediated by the accumulation of
reactive oxygen species (ROS) highlighting a potent
oxidant role of this molecule. These studies suggest the potential
therapeutic effects of Centaurea ainetensis, and its component,
Salograviolide A, against epidermal squamous cell
carcinogenesis.