Melatonin suppresses the metastatic potential of osteoblastic prostate cancers by inhibiting integrin α2 β1 expression

J Pineal Res. 2022 Apr;72(3):e12793. doi: 10.1111/jpi.12793. Epub 2022 Mar 10.

Abstract

Advanced prostate cancer often develops into bone metastasis, which is characterized by aberrant bone formation with chronic pain and lower chances of survival. No treatment exists as yet for osteoblastic bone metastasis in prostate cancer. The indolamine melatonin (N-acetyl-5-methoxytryptamine) is a major regulator of the circadian rhythm. Melatonin has shown antiproliferative and antimetastatic activities but has not yet been shown to be active in osteoblastic bone lesions of prostate cancer. Our study investigations reveal that melatonin concentration-dependently decreases the migratory and invasive abilities of two osteoblastic prostate cancer cell lines by inhibiting FAK, c-Src, and NF-κB transcriptional activity via the melatonin MT1 receptor, which effectively inhibits integrin α2 β1 expression. Melatonin therapy appears to offer therapeutic possibilities for reducing osteoblastic bone lesions in prostate cancer.

Keywords: MT1 receptor; bone metastasis; integrin; melatonin; osteoblastic prostate cancer.

MeSH terms

  • Cell Line, Tumor
  • Humans
  • Integrin alpha2beta1 / therapeutic use
  • Male
  • Melatonin* / pharmacology
  • Melatonin* / therapeutic use
  • NF-kappa B / metabolism
  • Prostatic Neoplasms* / metabolism

Substances

  • Integrin alpha2beta1
  • NF-kappa B
  • Melatonin