Melatonin suppresses the metastatic potential of osteoblastic prostate cancers by inhibiting integrin α<sub>2</sub>β<sub>1</sub> expression
Huai‐Ching Tai, Shih‐Wei Wang, Sanskruti Swain, Liang‐Wei Lin, Hsiao‐Chi Tsai, Shan‐Chi Liu, Hsi‐Chin Wu, Jeng‐Hung Guo, Chunlin Liu, Yu‐Wei Lai, Tien‐Huang Lin, Shun‐Fa Yang, Chih‐Hsin Tang
Abstract
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 MT 1 receptor, which effectively inhibits integrin α 2 β 1 expression. Melatonin therapy appears to offer therapeutic possibilities for reducing osteoblastic bone lesions in prostate cancer.