Curcumin suppresses the growth and metastasis of prostate cancer cells by downregulation of Skp2

Yuanying Gong, Wenfu Lu, Yingqiu Xie, Qing Yang, Robert J. Matusik, Zhenbang Chen

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Background. Aberrant overexpression of Skp2 is frequently found in human cancers including prostate cancer, but little is known about pharmacological compounds targeting Skp2 activity. This study investigated inhibitory effects of curcumin (diferuloylmethane) on malignant features of prostate cancer cells in vitro, xenograft mouse models in vivo, and mechanistically on Skp2 level. Methods. Prostate cancer cells (PC3) and mouse prostate cancers cells (MPC3) cultured in petri dishes were treated with curcumin solution for indicated periods of time in vitro. Quantitative real-time reverse-transcription polymerase chain reaction (qRTPCR) and Western blot analyses were used to determine mRNA and protein expression of Skp2 in cancer cells. Cell proliferation, colony formation, and invasion assay were compared between curcumin-treated and control cells. Mouse prostate cancer cells were injected into immunodeficient mice followed with curcumin administration (200mg/kg/day). Tumorigenesis was analyzed in curcumin-treated and control mice after 20 days. Results. Curcumin treatment of PC3 cells resulted in a significant reduction of cell proliferation, soft agar transformation and invasion as compared to controls. Curcumin treatment led to a decrease of Skp2 level through a reduction of Skp2 mRNA and a shortened half-life of Skp2 protein. As expected, p27 protein, a major downstream target of Skp2, was increased upon curcumin treatment, whereas c-Myc protein level was not affected by curcumin treatment in prostate cancer cells. MPC3 cells, administered into immunodeficient mice via tail vein or orthotopic implantation, developed lung metastasis or enlarged prostate tumors. Importantly, cancer progression was significantly suppressed by curcumin treatment. A reduced level of Skp2 protein and induction of cell senescence were detected in tumors of curcumin-treated mice, but not in tumors of control mice. Conclusion. Our results indicated that curcumin suppresses both the tumor growth in mouse prostates and distant metastasis of prostate cancer cells in lung by inhibiting Skp2 level.

Original languageEnglish
Title of host publicationProstate Cancer Cells
Subtitle of host publicationDetection, Growth and Treatment
PublisherNova Science Publishers, Inc.
Pages87-102
Number of pages16
ISBN (Print)9781622575251
Publication statusPublished - Dec 1 2012

Keywords

  • Curcumin
  • Prostate cancer
  • Skp2

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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    Gong, Y., Lu, W., Xie, Y., Yang, Q., Matusik, R. J., & Chen, Z. (2012). Curcumin suppresses the growth and metastasis of prostate cancer cells by downregulation of Skp2. In Prostate Cancer Cells: Detection, Growth and Treatment (pp. 87-102). Nova Science Publishers, Inc..