Luk G D, Civin C I, Weissman R M, Baylin S B
Science. 1982 Apr 2;216(4541):75-7. doi: 10.1126/science.6950518.
The ornithine decarboxylase inhibitor DL-alpha-difluoromethyl ornithine inhibited a proliferation-associated increase in ornithine decarboxylase activity in cultured human promyelocytic leukemia cells, resulting in a marked suppression of cell proliferation and subsequent cell loss. It also inhibited increases in ornithine decarboxylase activity associated with the phorbol ester-induced conversion of promyelocytic HL-60 cells to monocyte-like cells and the retinoic acid-induced conversion to granulocyte-like cells. However, the inhibition of ornithine decarboxylase activity did not prevent cellular differentiation. These results suggest that polyamine biosynthesis has a specific role in cell proliferation rather than in inducing differentiation that is not accompanied by proliferation. The data also demonstrate that cessation of proliferation in HL-60 cells is not necessarily associated with differentiation.
鸟氨酸脱羧酶抑制剂DL-α-二氟甲基鸟氨酸抑制了培养的人早幼粒细胞白血病细胞中与增殖相关的鸟氨酸脱羧酶活性增加,导致细胞增殖明显受抑并随后出现细胞丢失。它还抑制了与佛波酯诱导早幼粒细胞HL-60细胞向单核细胞样细胞转化以及视黄酸诱导向粒细胞样细胞转化相关的鸟氨酸脱羧酶活性增加。然而,对鸟氨酸脱羧酶活性的抑制并未阻止细胞分化。这些结果表明,多胺生物合成在细胞增殖中具有特定作用,而非在不伴有增殖的诱导分化中起作用。数据还表明,HL-60细胞增殖的停止不一定与分化相关。