Melatonin interrupts osteoclast functioning and suppresses tumor-secreted RANKL expression: implications for bone metastases

Po I. Liu, An Chen Chang, Jiun Lin Lai, Tien Huang Lin, Chun Hao Tsai, Po Chun Chen, Ya Jing Jiang, Liang Wei Lin, Wei Chien Huang, Shun Fa Yang, Chih Hsin Tang

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37 引文 斯高帕斯(Scopus)

摘要

Cancer-related bone erosion occurs frequently in bone metastasis and is associated with severe complications such as chronic bone pain, fractures, and lower survival rates. In recognition of the fact that the darkness hormone melatonin is capable of regulating bone homeostasis, we explored its therapeutic potential in bone metastasis. We found that melatonin directly reduces osteoclast differentiation, bone resorption activity and promotes apoptosis of mature osteoclasts. We also observed that melatonin inhibits RANKL production in lung and prostate cancer cells by downregulating the p38 MAPK pathway, which in turn prevents cancer-associated osteoclast differentiation. In lung and prostate bone metastasis models, twice-weekly melatonin treatment markedly reduced tumor volumes and numbers of osteolytic lesions. Melatonin also substantially lowered the numbers of TRAP-positive osteoclasts in tibia bone marrow and RANKL expression in tumor tissue. These findings show promise for melatonin in the treatment of bone metastases.
原文英語
頁(從 - 到)1503-1515
頁數13
期刊Oncogene
40
發行號8
DOIs
出版狀態已發佈 - 2月 25 2021
對外發佈

ASJC Scopus subject areas

  • 分子生物學
  • 遺傳學
  • 癌症研究

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