Lupane triterpenes were found to promote melanogenesis, a hallmark of B16 2F2 mouse
melanoma cell differentiation. Studies of the structure-activity relationships demonstrated that the keto function at C-3 of the
lupane skeleton played important roles in the melanogenic activities of
lupane triterpenes on
melanoma cells. The carbonyl group at C-17 of
lupane triterpenes was essential against their apoptosis-inducing activity against human
cancer cells via the inhibition of
topoisomerase I. We investigated whether signaling mechanisms were involved in the stimulative effects of
lupane triterpenes on the melanogenesis of B16 2F2 cells. In experiments using selective inhibitors against various signal transduction molecules and Western blotting analysis, it was suggested that
p38 MAPK was involved in
melanoma cell differentiation as a downstream effector of PKA.
Lupeol (compound 1), a
lupane triterpene, induced dendrite formations, a morphological hallmark of B16 2F2 cell differentiation by rearrangement of the actin cytoskeleton. The activation of
cofilin, an
actin depolymerizing factor, by compound 1 caused actin fiber disassembly in B16 2F2 cells. Furthermore, compound 1 was shown to inhibit the cell motilities of human
melanoma and
neuroblastoma in vitro.