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SMILE upregulated by metformin inhibits the function of androgen receptor in prostate cancer cells

Seung-Yon Lee1, Chin-Hee Song1, Yuan-Bin Xie1

  • 1Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University, Gwangju 500-757, Republic of Korea.

Cancer Letters
|September 10, 2014
PubMed

Insights

Metformin, a diabetes drug, inhibits prostate cancer growth by targeting the androgen receptor (AR). It upregulates SMILE, a protein that suppresses AR activity, thereby reducing cancer cell proliferation.

Area of Science:

  • Oncology
  • Endocrinology
  • Molecular Biology

Background:

  • Metformin, a widely used diabetes medication, has shown potential in inhibiting prostate cancer cell growth.
  • The androgen receptor (AR) is a critical factor in the proliferation of prostate cancer cells.

Purpose of the Study:

  • To investigate the effect of metformin on androgen receptor (AR) function in prostate cancer cells.
  • To elucidate the mechanism by which metformin inhibits AR-mediated prostate cancer cell proliferation.

Main Methods:

  • Investigated metformin's effect on AR function and target gene expression in LNCaP and C4-2 prostate cancer cells.
  • Examined the role of small heterodimer partner-interacting leucine zipper (SMILE) in mediating metformin's effects.
  • Utilized shRNA to knock down SMILE expression and assessed its impact on AR function and cell growth.

Main Results:

  • Metformin inhibited androgen-dependent prostate cancer cell growth and AR target gene expression.
  • Metformin upregulated SMILE protein levels, and SMILE knockdown abolished metformin's inhibitory effect.
  • SMILE protein directly suppressed AR transactivation, interacted with AR, and competed with the coactivator SRC-1.

Conclusions:

  • SMILE acts as a novel AR corepressor induced by metformin.
  • SMILE mediates the inhibitory effect of metformin on androgen-dependent prostate cancer cell growth.
  • Metformin's potential as a therapeutic agent for prostate cancer warrants further investigation.
Keywords:
Androgen receptorCorepressorMetforminProstate cancer cellsSMILE

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