Sarcodiol (SD) is a semi-synthetic derivative of
sarcophine, a marine
natural product. In our previous work, we reported the significant chemopreventive effects of SD against non-
melanoma skin cancer both in vitro and in vivo mouse models. In this investigation, we extended this work to study the effect of sarcodiol on
melanoma development, the more deadly form of
skin cancer, using the mouse
melanoma B₁₆F₁₀ cell line. In this study we report that SD inhibits the de novo
DNA synthesis and enhances fragmentation of
DNA. We also evaluated the antitumor effect of SD on
melanoma cell viability using several
biomarkers for cell proliferation and apoptosis. SD inhibits the expression levels of signal transducers and activators of transcription
protein (STAT-3) and
cyclin D1, an activator of
cyclin-dependent kinase 4 (Cdk4). SD treatment also enhances cellular level of
tumor suppressor protein 53 (p53) and stimulates cleavage of the nuclear
poly (ADP-ribose) polymerase (cleaved-PARP). SD also enhances cellular levels of cleaved
Caspase-3, -8, -9 and stimulates enzymatic activities of
Caspase-3, -8 and -9. These results, in addition to inhibition of cell viability, suggest that SD inhibits
melanoma cell proliferation by arresting the cell-division cycle in a Go quiescent phase and activates programmed cell death (apoptosis) via extrinsic and intrinsic pathways. Finally, these studies demonstrate that SD shows a very promising chemopreventive effect in
melanoma B₁₆F₁₀
tumor cells.