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Sensitivity of TP53-Mutated Cancer Cells to the Phytoestrogen Genistein Is Associated With Direct Inhibition of Plk1 Activity

Title
Sensitivity of TP53-Mutated Cancer Cells to the Phytoestrogen Genistein Is Associated With Direct Inhibition of Plk1 Activity
Author
임형신
Keywords
POLO-LIKE-KINASE; UP-REGULATION; TRANSCRIPTIONAL INHIBITION; CYCLE PROGRESSION; CARCINOMA CELLS; MITOTIC ARREST; TUMOR-GROWTH; DNA-DAMAGE; EXPRESSION; APOPTOSIS
Issue Date
2017-10
Publisher
WILEY-BLACKWELL
Citation
JOURNAL OF CELLULAR PHYSIOLOGY, v. 232, No. 10, Page. 2818-2828
Abstract
Polo-like kinase 1 (Plk1), a conserved Ser/Thr mitotic kinase, has been identified as a promising target for anticancer drug development because its overexpression is correlated with malignancy. Here, we found that genistein, an isoflavone, inhibits Plk1 kinase activity directly. Previously the mitotic disturbance phenomenon induced by treatment with genistein was not fully explained by its inhibitory effect on EGFR. In kinase profiling assays, it showed selectivity relative to a panel of kinases, including EGFR. Treatment with genistein induced cell death in a concentration-dependent manner in cancer cells from diverse tissue origins, but not in non-transformed cells such as hTERT-RPE or MCF10A cells. We also observed that genistein tended to be more selective against cancer cells with mutations in the TP53 gene. TP53-depeleted LNCaP and NCI-H460 cells using shRNA targeting human TP53 were more sensitive to cell death by treatment of genistein. Furthermore, genistein induced mitotic arrest by inhibiting Plk1 activity and, consequently, led to mitotic catastrophe and apoptosis. These data suggest that genistein may be a promising anticancer drug candidate due to its inhibitory activity against Plk1 as well as EGFR and effectiveness toward cancer cells, especially those with p53-mutation.
URI
https://onlinelibrary.wiley.com/doi/abs/10.1002/jcp.25680https://repository.hanyang.ac.kr/handle/20.500.11754/103700
ISSN
1097-4652; 0021-9541
DOI
10.1002/jcp.25680
Appears in Collections:
COLLEGE OF PHARMACY[E](약학대학) > PHARMACY(약학과) > Articles
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