Melatonin as a therapeutic agent for the inhibition of hypoxia-induced tumor progression: A description of possible mechanisms involved

Sepideh Bastani, Moloud Akbarzadeh, Yeganeh Rastgar Rezaei, Ali Farzane, Mohammad Nouri, Mahsa Mollapour Sisakht, Amir Fattahi, Maryam Akbarzadeh, Russel J. Reiter

Research output: Contribution to journalReview articlepeer-review

Abstract

Hypoxia has an important role in tumor progression via the up-regulation of growth factors and cellular adaptation genes. These changes promote cell survival, proliferation, invasion, metastasis, angiogenesis, and energy metabolism in favor of cancer development. Hypoxia also plays a central role in determining the resistance of tumors to chemotherapy. Hypoxia of the tumor microenvironment provides an opportunity to develop new therapeutic strategies that may selectively induce apoptosis of the hypoxic cancer cells. Melatonin is well known for its role in the regulation of circadian rhythms and seasonal reproduction. Numerous studies have also documented the anti-cancer properties of melatonin, including anti-proliferation, anti-angiogenesis, and apoptosis promotion. In this paper, we hypothesized that melatonin exerts anti-cancer effects by inhibiting hypoxia-induced pathways. Considering this action, co-administration of melatonin in combination with other therapeutic medications might increase the effectiveness of anti-cancer drugs. In this review, we discussed the possible signaling pathways by which melatonin inhibits hypoxia-induced cancer cell survival, invasion, migration, and metabolism, as well as tumor angiogenesis.

Original languageEnglish (US)
Article number10874
JournalInternational journal of molecular sciences
Volume22
Issue number19
DOIs
StatePublished - Oct 1 2021

Keywords

  • Angiogenesis
  • Antioxidant
  • Apoptosis
  • Cancer
  • Melatonin
  • Metastasis

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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