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Esculetin Inhibits the Survival of Human Prostate Cancer Cells by Inducing Apoptosis and Arresting the Cell Cycle.

ABSTRACT: Background:Prostate cancer (PCa) is one of the most important causes of death in men and thus new therapeutic approaches are needed. In this study, antiproliferative and anti-migration properties of a coumarin derivative esculetin were evaluated. Methods:Human PCa cell lines PC3, DU145, and LNCaP were treated with various concentrations of esculetin for 24 to 72 hours, and cell viability was determined by the MTT test. Cell cycle and apoptosis were analyzed by using cell-based cytometer. Gene expression levels were assessed by reverse transcription and quantitative real-time PCR, cell migration was determined by the wound healing assay. The protein expression was measured by Western blotting. Results:Esculetin inhibited cell proliferation in a dose- and time-dependent manner. Cell migration was inhibited by esculetin treatment. Administration of esculetin significantly reduced the cells survival, induced apoptosis and caused the G1 phase cell cycle arrest shown by image-based cytometer. The induced expression of cytochrome c, p53, p21 and p27, and down-regulated CDK2 and CDK4 may be the underlying molecular mechanisms of esculetin effect. Esculetin suppressed phosphorylation of Akt and enhanced protein expression of tumor-suppressor phosphatase and tensin homologue. Conclusions:Our findings showed that the coumarin derivative esculetin could be used in the management of PCa. However, further in vivo research is needed.

SUBMITTER: Turkekul K

PROVIDER: S-EPMC5886490 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Esculetin Inhibits the Survival of Human Prostate Cancer Cells by Inducing Apoptosis and Arresting the Cell Cycle.

Turkekul Kader K Colpan R Dilsu RD Baykul Talha T Ozdemir Mehmet D MD Erdogan Suat S

Journal of cancer prevention 20180330 1

<h4>Background</h4>Prostate cancer (PCa) is one of the most important causes of death in men and thus new therapeutic approaches are needed. In this study, antiproliferative and anti-migration properties of a coumarin derivative esculetin were evaluated.<h4>Methods</h4>Human PCa cell lines PC3, DU145, and LNCaP were treated with various concentrations of esculetin for 24 to 72 hours, and cell viability was determined by the MTT test. Cell cycle and apoptosis were analyzed by using cell-based cyt ...[more]

PMID: 29629344

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Project description:Prostate cancer (PCa) remains a leading cause of mortality among men in the United States and Western Europe. The molecular mechanism of PCa pathogenesis has not been fully elucidated. In the present study, the expression profile of E2F transcription factor 7 (E2F7) in PCa was examined using immunohistochemistry and reverse transcription‑quantitative PCR, whilst cell cycle progression and apoptosis were determined using fluorescent cell activated sorting techniques. Cell viability was measured using Cell Counting Kit‑8 in loss‑ and gain‑of‑function studies. Dual‑luciferase reporter assay was used to verify if E2F7 was one of the potential targets of miR‑30c. The staining score of E2F7 of PCa tissues was found to be notably higher compared with that of adjacent normal tissues. Suppression of E2F7 expression in PCa cell lines led to significantly reduced proliferation rates, increased proportion of cells in the G1 phase of the cell cycle and higher apoptotic rates compared with those in negative control groups. Dual‑luciferase reporter assay revealed E2F7 to be one of the binding targets of microRNA (miR)‑30c. In addition, transfection of miR‑30c mimics into PCa cells resulted in reduced cell viability, increased proportion of cells in the G1 phase and higher apoptotic rates. By contrast, transfection with the miR‑30c inhibitor led to lower apoptosis rates of PCa cells compared with negative control groups, whilst E2F7 siRNA co‑transfection reversed stimulatory effects of miR‑30c inhibitors on cell viability. In addition, the expression of cyclin‑dependent kinase inhibitor p21 were found to be upregulated by transfection with either E2F7 siRNA or miR‑30c mimics into PCa cells. In conclusion, the present study suggested that E2F7 may be positively associated with PCa cell proliferation by inhibiting p21, whereas E2F7 is in turn under regulation by miR‑30c. These observations suggest the miR‑30c/E2F7/p21 axis to be a viable therapeutic target for PCa.

Dataset Information

Esculetin Inhibits the Survival of Human Prostate Cancer Cells by Inducing Apoptosis and Arresting the Cell Cycle.

Publications

Esculetin Inhibits the Survival of Human Prostate Cancer Cells by Inducing Apoptosis and Arresting the Cell Cycle.

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