PHORBOL ESTER-INDUCED, CELL-CYCLE-SPECIFIC, GROWTH-INHIBITION OF HUMAN B-LYMPHOMA CELL-LINES

PHORBOL ESTER-INDUCED, CELL-CYCLE-SPECIFIC, GROWTH-INHIBITION OF HUMAN B-LYMPHOMA CELL-LINES
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DOI:
10.1093/jnci/82.6.501
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发表时间:
1990-03-21
影响因子:
10.3
通讯作者:
URBA, WJ
URBA, WJ
中科院分区:
医学1区
文献类型:
--
作者:
BECKWITH, M;LONGO, DL;URBA, WJ

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在用蛋白激酶 C 激活佛波酯处理后,检查了三种 B 细胞和一种非 B 细胞来源的人淋巴瘤细胞系的激活、生长和分化。这些药物的治疗导致了与正常 B 细胞中观察到的类似的早期激活事件。然而,与它们对正常人 B 淋巴细胞的生长促进作用相反,接触这些佛波酯可诱导三种 B 细胞来源的淋巴瘤系的深度生长抑制。培养开始后 24 小时内即可达到最大抑制作用,如果在培养 12 小时(而不是 20 小时)后去除佛波酯,则可以逆转。佛波酯处理的淋巴瘤细胞的细胞周期分析显示,一个细胞系中存在 G1/S 阻滞,而其他两个细胞系中的细胞则积聚在 G2/M 期。这些数据表明,蛋白激酶 C 结合佛波酯可以在活跃分裂的人 B 淋巴瘤细胞的两个位置中断细胞周期。这些发现可能对人类恶性淋巴瘤的潜在治疗有价值。
The activation, growth, and differentiation of three B-cell- and one non-B-cell derived human lymphoma cell lines were examined after treatment with protein kinase C-activating phorbol esters. Treatment with these agents resulted in early activation events similar to those observed in normal B cells. However, in contrast to their growth-promoting effect on normal human B lymphocytes, exposure to these phorbol esters induced profound growth inhibition of the three B-cell-derived lymphoma lines. Maximal inhibition was achieved within 24 hours of culture initiation and could be reversed if the phorbol ester was removed after 12, but not 20, hours in culture. Cell-cycle analysis of phorbol ester-treated lymphoma cells revealed a G1/S block in one line, whereas cells from the other two lines accumulated in G2/M. These data demonstrate that protein kinase C-binding phorbol esters can interrupt the cell cycle intwo places in actively dividing human B-lymphoma cells. These findings may prove valuable with regard to potential therapy of human malignant lymphomas.