Mechanisms of action of the novel sulfonamide anticancer agent E7070 on cell cycle progression in human non-small cell lung cancer cells

被引:115
作者
Fukuoka, K
Usuda, J
Iwamoto, Y
Fukumoto, H
Nakamura, T
Yoneda, T
Narita, N
Saijo, N
Nishio, K
机构
[1] Natl Canc Ctr, Res Inst, Div Pharmacol, Chuo Ku, Tokyo 1040045, Japan
[2] Nara Med Univ, Dept Internal Med 2, Kashihara, Nara 634, Japan
关键词
sulfonamide; E7070; cell cycle; G1; arrest; lung cancer cells; resistant cells;
D O I
10.1023/A:1010608317361
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
E7070 is a novel sulfonamide antitumor agent that exhibits potent antitumor activity in vitro and in vivo. This compound affects cell cycle progression in human tumor cells. To elucidate the mechanisms by which E7070 inhibits tumor cell growth, we established and characterized an E7070-resistant subline, A549/ER, from a human non-small cell lung cancer cell line A549. Flow cytometric analyses demonstrated an increase in G0/G1 and a decrease in S phase populations in cells treated with E7070 at 20 or 100 mug/ml for 24 h. Longer exposure to E7070, i.e. 48 and 72 h, increased the G2/M phase fraction in A549 cells. These inhibitory actions of E7070 on cell cycle progression were not observed in A549/ER cells. E7070 inhibited the phosphorylation of pRb, decreased expressions of cyclin A, B1, CDK2, and CDC2 proteins, and suppressed CDK2 catalytic activity with the induction of p53 and p21 proteins in A549 cells but not in A549/ER cells. Taken together, these results suggest that E7070 exerts its antitumor effects by disturbing the cell cycle at multiple points, including both the G1/S and the G2/M transition, in human lung cancer cells.
引用
收藏
页码:219 / 227
页数:9
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