Dynamic color-coded fluorescence imaging of the cell-cycle phase, mitosis, and apoptosis demonstrates how caffeine modulates cisplatinum efficacy.
Dynamic color-coded fluorescence imaging of the cell-cycle phase, mitosis, and apoptosis demonstrates how caffeine modulates cisplatinum efficacy.
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细胞周期阶段、有丝分裂和细胞凋亡的动态颜色编码荧光成像展示了咖啡因如何调节顺铂功效。
DOI：
10.1002/jcb.24593
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发表时间：
2013
影响因子：
4
通讯作者：
Hoffman,RobertM
中科院分区：
文献类型：
--
作者：
Miwa,Shinji;Yano,Shuya;Tome,Yasunori;Sugimoto,Naotoshi;Hiroshima,Yukihiko;Uehara,Fuminari;Mii,Sumiyuki;Kimura,Hiroaki;Hayashi,Katsuhiro;Efimova,ElenaV;Fujiwara,Toshiyoshi;Tsuchiya,Hiroyuki;Hoffman,RobertM
咖啡因可以增强某些抗癌药物的效果，但其调节机制尚不清楚。在这项研究中，通过真实的时间荧光蛋白成像，在亚细胞水平上观察了咖啡因诱导的顺铂疗效调节。通过对143 B人骨肉瘤双色细胞成像观察到有丝分裂和凋亡变化，其中GFP在细胞核中表达，RFP在细胞质中表达。使用在细胞核中表达基于荧光泛素化的细胞周期指示剂（FUCCI）的HeLa细胞的延时成像来成像细胞周期的调节。克隆形成实验表明，咖啡因可增强顺铂对细胞增殖的抑制作用。亚细胞成像显示顺铂可抑制143 B细胞的有丝分裂并诱导其凋亡。顺铂和咖啡因的组合增强有丝分裂，随后增加凋亡。延时成像显示，顺铂强烈诱导HeLa‐FUCCI细胞的S/G2期细胞周期停滞。咖啡因克服了顺铂诱导的细胞周期阻滞，从而提高了其疗效，因为顺铂对静止细胞无效。本报告中的数据表明，咖啡因调节癌细胞的细胞周期，从而增强顺铂等细胞周期依赖性抗癌药物的疗效。J.细胞。114：2454-2460，2013.© 2013 Wiley Periodicals，Inc.
Caffeine enhances the effect of certain anticancer drugs, but the mechanism of modulation is poorly understood. In this study, modulation of cisplatinum efficacy induced by caffeine was visualized at the subcellular level by real‐time fluorescent‐protein imaging. Mitotic and apoptotic changes were observed by imaging 143B human osteosarcoma dual‐color cells, in which GFP is expressed in the nucleus and RFP is expressed in the cytoplasm. Modulation of the cell cycle was imaged using time‐lapse imaging of HeLa cells expressing a fluorescent ubiquitination‐based cell cycle indicator (FUCCI) in the nucleus. Clonogenic assays showed that caffeine increased the inhibition by cisplatinum on cell proliferation. Subcellular imaging demonstrated that cisplatinum decreased mitosis and induced apoptosis in 143B cells. The combination of cisplatinum and caffeine enhanced mitosis and subsequently increased apoptosis. Time‐lapse imaging showed that cisplatinum strongly induced cell‐cycle arrest in the S/G2phase in HeLa‐FUCCI cells. Caffeine overcame the cell‐cycle arrest induced by cisplatinum, thereby increasing its efficacy, since cisplatinum is ineffective against quiescent cells. The data in this report indicate that caffeine modulates the cell cycle in cancer cells, thereby enhancing efficacy of cell‐cycle‐dependent anticancer drugs such as cisplatinum. J. Cell. Biochem. 114: 2454–2460, 2013. © 2013 Wiley Periodicals, Inc.
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10.1016/s0021-9258(19)45480-x
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DOI：
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期刊：
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