Control of phenotypic expression of cultured B16 melanoma cells by plant glycosides

The effects of two plant glycosides, ginsenosides Rh1 and Rh2, on the growth and differentiation of mouse melanoma (B16) cells in culture were studied. These plant glycosides have a dammarane skeleton resembling a steroid skeleton as an aglycone. Ginsenoside Rh2 inhibits the growth of B16 melanoma cells, causes morphological alterations, and stimulates melanogenesis at high cellular density. When ginsenoside Rh2 was removed after 2 or 6 days of treatment, the growth rate recovered slightly but not completely, during the period of observation (4 days after removal). On the other hand, ginsenoside Rh1 does not inhibit the growth of melanoma cells even at concentrations over 100 microM but stimulates the expression of the melanotic phenotype. Ginsenosides Rh1 and Rh2, possessing a glucose molecule at C-6 and C-3, respectively, have very similar chemical structures, but their effects on B16 melanoma cells differ remarkably. While it appears that the degree of differentiation is inversely related to cell growth, the present observations suggest that the differentiation and growth capacity of this B16 melanoma subline are independent phenotypic expressions.