Stimulation of melanogenesis in a human melanoma cell line by bistratene A

The polyether toxin, bistratene A, induced morphological and functional differentiation of a human melanoma cell line (MM96E). The cells became blocked at the G2/M transition and elaborated a number of processes. Tyrosinase activity and melanin content were substantially increased. Northern blot analysis showed up-regulation of mRNA for several genes known to be involved in melanin biosynthesis (pmel17, pmel34, and tyrosinase related proteins, TRP-1 and TRP-2). Bistratene A induced the phosphorylation of several proteins as assessed by 2D gel electrophoresis and one of these was identified as stathmin (oncoprotein 18), a cell-cycle regulated phosphoprotein. Bistratene A specifically induced the translocation of protein kinase Cdelta (PKCdelta) from a soluble to a particulate fraction without affecting other isoforms. These results implicate a role for protein kinase Cdelta in the induction of differentiation of this human melanoma cell line.