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Melatonin: a natural guardian in cancer treatment

Yurou Cao1, Hang Zhang1, Xubin Chen2

  • 1School of Stomatology, Hainan Medical University and Hainan Academy of Medical Sciences, Haikou, Hainan, China.

Frontiers in Pharmacology
|August 4, 2025
PubMed

Insights

Melatonin (MLT), a natural hormone, shows potent anticancer properties by inhibiting tumor growth and enhancing drug efficacy. Despite limitations like low bioavailability, targeted delivery offers future potential for cancer therapy.

Area of Science:

  • Endocrinology
  • Oncology
  • Pharmacology

Background:

  • Melatonin (MLT), a pineal gland hormone, possesses significant anticancer properties.
  • MLT exhibits antioxidant, anti-proliferative, anti-angiogenic, and pro-apoptotic functions.
  • Its anticancer mechanisms involve epigenetic regulation, metabolic reprogramming, immune modulation, and PI3K/AKT pathway signaling.

Purpose of the Study:

  • To review the anticancer effects of melatonin.
  • To explore the mechanisms underlying melatonin's antitumor activity.
  • To discuss the potential of melatonin in combination cancer therapy and future clinical applications.

Main Methods:

  • Literature review of preclinical and clinical studies on melatonin's anticancer effects.
  • Analysis of studies investigating melatonin's mechanisms of action.
  • Evaluation of combination therapy studies involving melatonin and conventional anticancer drugs.

Main Results:

  • Melatonin demonstrates broad-spectrum anticancer activities, including inhibiting tumor cell proliferation, migration, and angiogenesis, while inducing apoptosis.
  • Key mechanisms include epigenetic modifications, metabolic reprogramming, immune micro-environment modulation, and regulation of the PI3K/AKT pathway.
  • Melatonin significantly potentiates the efficacy of chemotherapeutic agents like cisplatin, 5-fluorouracil, and paclitaxel.
  • Challenges such as low bioavailability and rapid metabolism limit clinical use, but are being addressed by targeted delivery and individualized therapy.

Conclusions:

  • Melatonin is a promising natural compound with multifaceted anticancer effects.
  • Combination therapy with melatonin may enhance treatment outcomes for various cancers.
  • Overcoming pharmacokinetic limitations through advanced delivery systems is crucial for realizing melatonin's full therapeutic potential in oncology.
Keywords:
anticancer activityantioxidant activitychemotherapy synergymelatonin (MLT)targeted delivery

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