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.
Watters
D
D
Queensland Cancer Fund Research Unit, Queensland Institute of Medical Research, P.O. Royal Brisbane Hospital, Australia. dianneW@qimr.edu.au
Garrone
B
B
Coomer
J
J
Johnson
W E
WE
Brown
G
G
Parsons
P
P
D000081:Acetamides; D000970:Antineoplastic Agents / Q000494:pharmacology*; D004790:Enzyme Induction; D004988:Ethers, Cyclic / Q000494:pharmacology*; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008543:Melanins / Q000096:biosynthesis*; D008545:Melanoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008938:Mitosis / Q000187:drug effects; D014442:Monophenol Monooxygenase / Q000096:biosynthesis; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D051745:Protein Kinase C-delta; D011714:Pyrans; D013141:Spiro Compounds; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured
D000081:Acetamides; D000970:Antineoplastic Agents; D004988:Ethers, Cyclic; D007527:Isoenzymes; D008543:Melanins; D011714:Pyrans; D013141:Spiro Compounds; C059975:bistratene A; D014442:Monophenol Monooxygenase; C497258:PRKCD protein, human; D011493:Protein Kinase C; D051745:Protein Kinase C-delta