Dehydroepiandrosterone inhibits B16 mouse melanoma cell growth by induction of differentiation.
BACKGROUND
Low serum concentrations of dehydroepiandrosterone (DHEA) and its sulfate are associated with an increased incidence of various human malignancies. DHEA has chemopreventive and antiproliferative effects in experimental studies. Accordingly, the effects of DHEA on B16 mouse melanoma cells were studied.


METHODS
The effects of DHEA on cell number and melanin production of the melanoma cells were measured. Specific DHEA receptor was detected by a cytosol binding assay. Protein kinase C (PKC) activity of the melanoma cells was detected by phosphorylation of PKC specific substrate.


RESULTS
DHEA dose-dependently inhibited the growth of melanoma cells and enhanced melanin production, which indicated the induction of differentiation. There was a [3H]DHEA specific binding protein in the melanoma cell cytosol. Although DHEA did not promote the translocation of PKC from the cytosolic to the membrane fraction, the total PKC activity was upregulated by treatment with DHEA.


CONCLUSIONS
DHEA inhibited the growth of B16 mouse melanoma cells by the induction of differentiation, possibly related to PKC upregulation mediated by DHEA receptor.
Kawai
S
S
Institute of Medical Science, St. Marianna University School of Medicine, Kawasaki, Japan.
Yahata
N
N
Nishida
S
S
Nagai
K
K
Mizushima
Y
Y
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002462:Cell Membrane / Q000201:enzymology; D003600:Cytosol / Q000201:enzymology; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D008543:Melanins / Q000096:biosynthesis; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000473:pathology; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009363:Neoplasm Proteins / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D016588:Anticarcinogenic Agents; D000970:Antineoplastic Agents; D008543:Melanins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D003687:Dehydroepiandrosterone; D003907:Dexamethasone; D011493:Protein Kinase C