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Sensitivity of TP53-Mutated Cancer Cells to the Phytoestrogen Genistein Is Associated With Direct Inhibition of Plk1 Activity.
Shin, Sol-Bi; Woo, Sang-Uk; Chin, Young-Won; Jang, Young-Joo; Yim, Hyungshin.
Afiliación
  • Shin SB; Department of Pharmacy, College of Pharmacy, Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan, Gyeonggi-do, Korea.
  • Woo SU; Department of Pharmacy, College of Pharmacy, Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan, Gyeonggi-do, Korea.
  • Chin YW; College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University-Seoul, Goyang, Gyeonggi-do, Korea.
  • Jang YJ; Department of Nanobiomedical Science and BK21 PLUS Global Research Center for Regenerative Medicine, Dankook University, Cheonan, Korea.
  • Yim H; Department of Pharmacy, College of Pharmacy, Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan, Gyeonggi-do, Korea.
J Cell Physiol ; 232(10): 2818-2828, 2017 Oct.
Article en En | MEDLINE | ID: mdl-27861885
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. J. Cell. Physiol. 232: 2818-2828, 2017. © 2016 Wiley Periodicals, Inc.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteína p53 Supresora de Tumor / Proteínas Proto-Oncogénicas / Proteínas Serina-Treonina Quinasas / Proteínas de Ciclo Celular / Antineoplásicos Hormonales / Genisteína / Inhibidores de Proteínas Quinasas / Fitoestrógenos / Proliferación Celular / Mutación Tipo de estudio: Diagnostic_studies / Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: J Cell Physiol Año: 2017 Tipo del documento: Article Pais de publicación: Estados Unidos
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteína p53 Supresora de Tumor / Proteínas Proto-Oncogénicas / Proteínas Serina-Treonina Quinasas / Proteínas de Ciclo Celular / Antineoplásicos Hormonales / Genisteína / Inhibidores de Proteínas Quinasas / Fitoestrógenos / Proliferación Celular / Mutación Tipo de estudio: Diagnostic_studies / Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: J Cell Physiol Año: 2017 Tipo del documento: Article Pais de publicación: Estados Unidos