Metformin targets c-MYC oncogene to prevent prostate cancer

Tunde Akinyeke, Satoko Matsumura, Xinying Wang, Yingjie Wu, Eric D. Schalfer, Anjana Saxena, Wenbo Yan, Susan K. Logan, Xin Li

Research output: Contribution to journalArticle

Abstract

Prostate cancer (PCa) is the second leading cause of cancerrelated death in American men and many PCa patients develop skeletal metastasis. Current treatment modalities for metastatic PCa are mostly palliative with poor prognosis. Epidemiological studies indicated that patients receiving the diabetic drug metformin have lower PCa risk and better prognosis, suggesting that metformin may have antineoplastic effects. The mechanism by which metformin acts as chemopreventive agent to impede PCa initiation and progression is unknown. The amplification of c-MYC oncogene plays a key role in early prostate epithelia cell transformation and PCa growth. The purpose of this study is to investigate the effect of metformin on c-myc expression and PCa progression. Our results demonstrated that (i) in Hi-Myc mice that display murine prostate neoplasia and highly resemble the progression of human prostate tumors, metformin attenuated the development of prostate intraepithelial neoplasia (PIN, the precancerous lesion of prostate) and PCa lesions. (ii) Metformin reduced c-myc protein levels in vivo and in vitro. In Myc-CaP mouse PCa cells, metformin decreased c-myc protein levels by at least 50%. (iii) Metformin selectively inhibited the growth of PCa cells by stimulating cell cycle arrest and apoptosis without affecting the growth of normal prostatic epithelial cells (RWPE-1). (iv) Reduced PIN formation by metformin was associated with reduced levels of androgen receptor and proliferation marker Ki-67 in Hi-Myc mouse prostate glands. Our novel findings suggest that by downregulating c-myc, metformin can act as a chemopreventive agent to restrict prostatic neoplasia initiation and transformation.

Original languageEnglish (US)
Pages (from-to)2823-2832
Number of pages10
JournalCarcinogenesis
Volume34
Issue number12
DOIs
StatePublished - Dec 2013

ASJC Scopus subject areas

  • Cancer Research

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    Akinyeke, T., Matsumura, S., Wang, X., Wu, Y., Schalfer, E. D., Saxena, A., Yan, W., Logan, S. K., & Li, X. (2013). Metformin targets c-MYC oncogene to prevent prostate cancer. Carcinogenesis, 34(12), 2823-2832. https://doi.org/10.1093/carcin/bgt307