A lymphocyte blastogenesis inhibitory factor (LBIF) reversibly arrests a human melanoma cell line, A375, at G1 and G2 phases of cell cycle.
A lymphocyte blastogenesis inhibitory factor, LBIF, has been found in the culture supernatant of a human macrophage-like cell line, U937. The factor has been purified by fast protein liquid chromatography. Partial amino acid sequencing analysis showed that LBIF was a novel immunoregulatory factor. Recent study has demonstrated that LBIF possesses a remarkable tumor growth inhibitory activity. In this study, the cell growth inhibitory activity of LBIF was characterized on the proliferation of a human melanoma cell line A375 in vitro. LBIF strongly inhibits the proliferation of A375 cells. The inhibitory activity was cytostatic and reversible by Day 5 although the lethal effect became apparent at Day 7. Cell cycle analysis by flow cytometry showed that LBIF arrested A375 cells at both G1 and G2/M phases. Mitotic index analysis indicated that A375 cells were arrested in G1 and G2 phases. LBIF function was not attributed to the elevation of intracytoplasmic cyclic-AMP levels. Thus, these results suggest that LBIF plays an important role in controlling cell cycle and there is a similarity between the mechanisms of G1 and G2 arrests in eukaryotic cell proliferation. LBIF-induced reversible cell-cycle arrest of A375 cells can be a useful system to analyze the signal transduction for cell proliferation and cell-cycle arrest.
Sugimura
K
K
Institute of Immunological Science, Hokkaido University, Sapporo, Japan.
Ohno
T
T
Wada
Y
Y
Ueda
Y
Y
Kimura
T
T
Azuma
I
I
D002455:Cell Division; D000242:Cyclic AMP / Q000378:metabolism; D004273:DNA, Neoplasm / Q000096:biosynthesis; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D007399:Interphase; D008222:Lymphokines / Q000494:pharmacology*; D008545:Melanoma / Q000378:metabolism / Q000473:pathology*; D008938:Mitosis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D006131:Growth Inhibitors; D008222:Lymphokines; D012334:RNA, Neoplasm; D000242:Cyclic AMP