Abstract:
The ethnomedicinal plant from the Cucurbitaceae family, Corallocarpus epigaeus, or its
bioactive derivatives have been widely utilized in traditional medicine owing to their distinct
applications against various human ailments and have lured the interest of ethnobotanists
and biochemists. Here, we report for the first time, the anti-cancer potential of a bio-active
fraction isolated from the dried rhizome of C. epigaeus, and the bioactive principle identified
as cucurbitacin B (Cu-B). The purification processes involving the utilization of multiple
organic extracts of C. epigaeus rhizome powder, yielded Cu-B from the Ethyl acetate
Cytotoxic Fraction (ECF), obtained by the chromatographic separation of the ethyl acetate
extract. Amongst the various cancer lines tested, melanoma cells exhibit maximal sensitivity
towards the Cu-B-containing ECF fraction. Cu-B induces an apoptotic mode of cell death
initiated intrinsically as well as extrinsically in A375 melanoma cells whilst remaining
comparatively less toxic to normal skin fibroblasts. In vivo studies involving a NOD-SCID
murine model of human melanoma demonstrate the ability of Cu-B to attenuate tumor
growth, while being pharmacologically safe in vivo, as assessed in Swiss albino mice.
Furthermore, Cu-B inhibits MEK 1/2 as well as the constitutive and EGF-induced ERK 1/2
activation, indicating a definitive involvement of MAPK signal transducers in regulating Cu-Bmediated anti-melanoma activity. Together, our study demonstrates the anti-melanoma
potential of C. epigaeus-derived Cu-B, which indicates the Cucurbitaceae succulent as a
prospective source for deriving potent and pharmacologically safe anti-cancer compounds
