title: Chk1 knockdown confers radiosensitization in prostate cancer stem cells.
abstract: Radioresistance is responsible for treatment failure after radiotherapy             in localized prostate cancer, while prostate cancer stem cells promote radioresistance             by preferential activation of the DNA damage response. Chk1 inhibition has been             shown to sensitize many tumor cells to radiation. However, whether Chk1 inhibition             can potentiate the cytotoxic effects of radiation on prostate cancer stem cells             remains to be elucidated. In this study, CD133+CD44+ cells were isolated using             microbeads and were found to possess cancer stem cell properties. Using shRNA,             Chk1 was knocked down in the sorted CD133+CD44+ cells. Our results demonstrated             that Chk1 knockdown abrogated the radiation-induced G2/M arrest, inhibited DNA             damage repair and promoted premature mitosis, leading to increased apoptosis in             the radiated sorted CD133+CD44+ cells. Moreover, these effects were accompanied             by caspase-2 activation and the inactivation of phosphorylated Cdc25C and Cdc2.             Our results suggest that Chk1 knockdown increases the radiosensitivity of CD133+CD44+             prostate cancer stem cells. Chk1 knockdown in prostate cancer stem cells may be             an effective therapeutic strategy against prostate cancer.
authors.affiliation: Department of Urology, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang 471003, PR China.
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Wang
authors.forename: Zhikun
authors.initials: Z
authors.lastname: Ma
authors.forename: Zheng
authors.initials: Z
authors.lastname: Xiao
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.forename: Zhongling
authors.initials: Z
authors.lastname: Dou
authors.forename: Xiaoshan
authors.initials: X
authors.lastname: Feng
authors.forename: Haijun
authors.initials: H
authors.lastname: Shi
mesh_terms: D000071916:AC133 Antigen; D015703:Antigens, CD; D017209:Apoptosis / Q000528:radiation effects; D016203:CDC2 Protein Kinase; D053143:Caspase 2 / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000528:radiation effects; D045744:Cell Line, Tumor; D000071877:Checkpoint Kinase 1; D019926:Cyclin B / Q000096:biosynthesis; D018844:Cyclin-Dependent Kinases; D004260:DNA Repair / Q000528:radiation effects*; D006023:Glycoproteins; D006801:Humans; D018960:Hyaluronan Receptors; D008297:Male; D008938:Mitosis / Q000528:radiation effects; D014411:Neoplastic Stem Cells / Q000528:radiation effects*; D010455:Peptides; D011471:Prostatic Neoplasms / Q000235:genetics*; D011494:Protein Kinases / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering; D011836:Radiation Tolerance / Q000235:genetics*; D020687:cdc25 Phosphatases / Q000096:biosynthesis
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D019926:Cyclin B; D006023:Glycoproteins; D018960:Hyaluronan Receptors; C000606023:PROM1 protein, human; D010455:Peptides; D034741:RNA, Small Interfering; D011494:Protein Kinases; C000605867:CHEK1 protein, human; D000071877:Checkpoint Kinase 1; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human; D018844:Cyclin-Dependent Kinases; C517009:CDC25C protein, human; D020687:cdc25 Phosphatases; D053143:Caspase 2