Summary The effect of LiCI on melanoma cell growth and differentiationl was studied in mouse and human melanoma cell lines. LiCI markedly inhibited B16 and HT-144 melanoma cell growth in iitro. Clonogenicity in soft agar of the melanoma cells was also markedly inhibited by LiCl. Pretreatmelnt of B16 mouse melanoma cells with LiCl delayed the appearance of melanoma tumours in syngeneic mice. Growth (Ptashne et al., 1980;Hori & Oka, 1979;Rybak & Stockdale, 1981). This agent also potentiated the mitogenic response of B and T cells (Hart 1981(Hart , 1982 Bray et al., '981).LiCl was found to modulate haematopoiesis by influencing pluripotential and committed stem cell proliferation and differentiation toward granulocytes (Gallicchio & Chen, 1981; Morley & Galbraith, 1978;Levitt & Quesenberg, 1980). Axolotl-embryo's ectodermal cells were induced to differentiate into mesenchyme, nerve cells and melanophores by LiCl (Lovtrop & Perris, 1983). LiCI has also been shown to potentiate the anti-melanoma effect of bleomycin in mice bearing melanoma tumours (Ballin et al., 1983).The biochemical basis of lithium's actions on cell growth and differentiation is unknown. However, in different tissues lithium has been shown to affect cyclic nucleotide levels (Dovsa & Mecher, 1970;Wang et al., 1974) glucose metabolism (Nordenberg et al., 1982; Dempsey et al., 1976) and phosphatidylinositol metabolism (Allison & Stewart, 1971; Allison et al., 1976; Berridge & Irvine, 1984 Cell growitth e:xperinments In most cases 105 cells were plated in 1.5ml culture medium, in 3.5cm culture dishes. When cells were cultured for more than 3 days, 3 x 104 cells were plated in 10ml culture medium in 8.5cm culture dishes. This was done to avoid cell crowding. Two to four hours later, after most cells were attached to the bottom of the petri dish, LiCI or myoinositol were added as indicated in legend to Figure 1 and
Guanosine is shown to potentiate markedly the antiproliferative effect of cytosine-beta-D-arabinoside (ara-C) on B16 F10 mouse and SKMEL-28 human melanoma cell lines. Several metabolic consequences of the synergistic interaction between ara-C and guanosine on cell growth were determined in B16 F10 mouse melanoma cells. Treatment of the cells with guanosine for 24 hr resulted in an increase in the percentage of cells in the S phase of the cell cycle, a threefold increase in intracellular GTP concentration, and an increase in the incorporation of ara-C into acid-insoluble material and phosphorylated metabolites. These findings suggest that guanosine potentiates the growth-inhibitory effect of ara-C in B16 F10 melanoma cells by increasing the intracellular concentration of its active metabolites.
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