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Genistein Enhances the Radiosensitivity of Breast Cancer Cells via G(2)/M Cell Cycle Arrest and Apoptosis

文献类型：期刊论文

作者Li, P5; Zhao, T5; Gong, L5; Li, Q5; Li, Q (reprint author), Chinese Acad Sci, Inst Modern Phys, Lanzhou 730000, Gansu, Peoples R China.; Liu, XX5; Sun, C5; Jin, XD5; Ye, F5
刊名MOLECULES
出版日期2013
卷号18页码:13200-13217
关键词Estrogen-receptor Dna-damage In-vitro Antiproliferative Properties Signaling Pathway Prostate-cancer P53 Family Tumorigenesis Supplements Mda-mb-231
ISSN号1420-3049
DOI10.3390/molecules181113200
英文摘要The aim of the present study was to investigate the radiosensitizing effect of genistein, and the corresponding mechanisms of action on breast cancer cells with different estrogen receptor (ER) status. Human breast cancer cell lines such as MCF-7 (ER-positive, harboring wild-type p53) and MDA-MB-231 (ER-negative, harboring mutant p53) were irradiated with X-rays in the presence or absence of genistein. Cell survival, DNA damage and repair, cell cycle distribution, cell apoptosis, expression of proteins related to G(2)/M cell cycle checkpoint and apoptosis were measured with colony formation assays, immunohistochemistry, flow cytometry and western blot analysis, respectively. Genistein showed relatively weak toxicity to both cell lines at concentrations in the range of 5-20 mu M. Using the dosage of 10 mu M genistein, the sensitizer enhancement ratios after exposure to X-rays at a 10% cell survival (IC10) were 1.43 for MCF-7 and 1.36 for MDA-MB-231 dcells, respectively. Significantly increased DNA damages, arrested cells at G(2)/M phase, decreased homologous recombination repair protein Rad51 foci formation and enhanced apoptotic rates were observed in both cell lines treated by genistein combined with X-rays compared with the irradiation alone. The combined treatment obviously up-regulated the phosphorylation of ATM, Chk2, Cdc25c and Cdc2, leading to permanent G(2)/M phase arrest, and up-regulated Bax and p73, down-regulated Bcl-2, finally induced mitochondria-mediated apoptosis in both cell lines. These results suggest that genistein induces G(2)/M arrest by the activation of the ATM/Chk2/Cdc25C/Cdc2 checkpoint pathway and ultimately enhances the radiosensitivity of both ER+ and ER- breast cancer cells through a mitochondria-mediated apoptosis pathway.
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WOS关键词ESTROGEN-RECEPTOR ; DNA-DAMAGE ; IN-VITRO ; ANTIPROLIFERATIVE PROPERTIES ; SIGNALING PATHWAY ; PROSTATE-CANCER ; P53 FAMILY ; TUMORIGENESIS ; SUPPLEMENTS ; MDA-MB-231
资助项目Gansu Provincial Funds for Distinguished Young Scholar[1111RJDA010]
WOS研究方向Biochemistry & Molecular Biology ; Chemistry
语种英语
WOS记录号WOS:000330311500006
出版者MDPI AG
资助机构Natural Science Foundation of Gansu province [096RJ2A033] ; Natural Science Foundation of Gansu province [096RJ2A033]
源URL[http://ir.impcas.ac.cn/handle/113462/18582]  
专题近代物理研究所_医学物理研究室
近代物理研究所_生物物理研究室
通讯作者Li, Q (reprint author), Chinese Acad Sci, Inst Modern Phys, Lanzhou 730000, Gansu, Peoples R China.
作者单位1.Shao, Shijun
2.[Cao, Linying] Univ Chinese Acad Sci, Beijing 100039, Peoples R China
3.[Wu, Qingfeng
4.Li, Qiang] Chinese Acad Sci, Inst Modern Phys, Lanzhou 730000, Peoples R China
5.[Cao, Linying
6.Shao, Shijun
7.Guo, Yong] Chinese Acad Sci, Lanzhou Inst Chem Phys, Key Lab Chem Northwestern Plant Resources, Lanzhou 730000, Peoples R China
8.[Cao, Linying
9.Guo, Yong] Chinese Acad Sci, Key Lab Nat Med Gansu Prov, Lanzhou Inst Chem Phys, Lanzhou 730000, Peoples R China
推荐引用方式
GB/T 7714		 Li, P,Zhao, T,Gong, L,et al. Genistein Enhances the Radiosensitivity of Breast Cancer Cells via G(2)/M Cell Cycle Arrest and Apoptosis[J]. MOLECULES,2013,18:13200-13217.
APA Li, P.,Zhao, T.,Gong, L.,Li, Q.,Li, Q .,...&Ye, F.(2013).Genistein Enhances the Radiosensitivity of Breast Cancer Cells via G(2)/M Cell Cycle Arrest and Apoptosis.MOLECULES,18,13200-13217.
MLA Li, P,et al."Genistein Enhances the Radiosensitivity of Breast Cancer Cells via G(2)/M Cell Cycle Arrest and Apoptosis".MOLECULES 18(2013):13200-13217.

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来源：近代物理研究所

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