Cotylenin A, a new differentiation inducer, and rapamycin cooperatively inhibit growth of cancer cells through induction of cyclin G2
Cotylenin A, a new differentiation inducer, and rapamycin cooperatively inhibit growth of cancer cells through induction of cyclin G2
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DOI：
10.1111/j.1349-7006.2008.00867.x
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发表时间：
2008-08-01
期刊：
影响因子：
5.7
通讯作者：
Honma, Yoshio
中科院分区：
文献类型：
--
作者：
Kasukabe, Takashi;Okabe-Kado, Junko;Honma, Yoshio
Cotylenin A是一种植物生长调节剂，雷帕霉素是一种哺乳动物雷帕霉素靶蛋白（mTOR）的抑制剂，是髓性白血病细胞分化的有效诱导剂。最近，我们发现Cotylenin A和雷帕霉素有效地抑制了包括MCF-7在内的几种人乳腺癌细胞系的增殖。在此，我们证明，在包括MCF-7细胞在内的几种癌细胞中，cotylenin A和雷帕霉素快速而显著地诱导细胞周期蛋白G2基因的表达。用Cotylenin A和雷帕霉素处理MCF-7细胞或在低血清培养基中培养诱导MCF-7细胞生长停滞在G1期，显著诱导cyclin G2基因表达。多柔比星、足叶乙甙和5-氟尿嘧啶等抗癌药物在诱导MCF-7细胞生长停滞于G1期或G2/M期的过程中也诱导了cyclin G2的表达。异位诱导的cyclin G2表达可有效抑制MCF-7细胞的增殖。此外，由细胞周期蛋白G2小干扰RNA诱导的细胞周期蛋白G2敲低显著降低了Cotylenin A加雷帕霉素诱导生长抑制的效力。两者合计，我们的研究结果表明，cotylenin A和雷帕霉素通过诱导细胞周期蛋白G2诱导癌细胞生长的抑制。
Cotylenin A, a plant growth regulator, and rapamycin, an inhibitor of mammalian target of rapamycin (mTOR), are potent inducers of differentiation of myeloid leukemia cells. Recently, we found that cotylenin A and rapamycin effectively inhibited the proliferation of several human breast cancer cell lines including MCF-7. Herein, we demonstrate that cotylenin A and rapamycin rapidly and markedly induced the cyclin G2 gene expression in several cancer cells including MCF-7 cells. The growth arrest of the MCF-7 cells at the G1 phase, induced by the treatment with cotylenin A and rapamycin or the culture in low serum medium, markedly induced the cyclin G2 gene expression. Anticancer drugs including doxorubicin, etoposide and 5-fluorouracil also induced cyclin G2 expression during induction of growth arrest of the MCF-7 cell at the G1 phase or G2/M phase. Ectopically inducible cyclin G2 expression potently inhibited the proliferation of MCF-7 cells. Furthermore, cyclin G2 knockdown induced by cyclin G2 small interfering RNA markedly reduced the potency of cotylenin A plus rapamycin to induce growth inhibition. Taken together, our results suggest that cotylenin A and rapamycin induce inhibition of cancer cell growth through the induction of cyclin G2.