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Volume 22
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Review

Melatonin as a Therapeutic Agent for the Inhibition of Hypoxia-Induced Tumor Progression: A Description of Possible Mechanisms Involved

by
Sepideh Bastani
1,2,
Moloud Akbarzadeh
2,3,
Yeganeh Rastgar Rezaei
4,
Ali Farzane
5,
Mohammad Nouri
6,
Mahsa Mollapour Sisakht
7,8,
Amir Fattahi
6,9,*,
Maryam Akbarzadeh
8,* and
Russel J. Reiter
10
1
Research Center for Pharmaceutical Nanotechnology (RCPN), Tabriz University of Medical Sciences, Tabriz 51368, Iran
2
Stem Cell And Regenerative Medicine Institute (SCARM), Tabriz University of Medical Sciences, Tabriz 51368, Iran
3
Department of Cellular and Molecular Biology, Faculty of Biological Science, Azarbaijan Shahid Madani University, Tabriz 51368, Iran
4
Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz 51368, Iran
5
Department of Health Information Management, School of Allied Medical Science, Tehran University of Medical Sciences, Tehran 11369, Iran
6
Department of Reproductive Biology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz 51368, Iran
7
Stem Cell and Regenerative Medicine Center of Excellence, Tehran University of Medical Sciences, Tehran 11369, Iran
8
Department of Biochemistry, Erasmus University Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands
9
Department of Obstetrics and Gynecology, Erlangen University Hospital, Friedrich-Alexander University of Erlangen–Nürnberg, Comprehensive Cancer Center ER-EMN, 91054 Erlangen, Germany
10
Department of Cell Systems and Anatomy, UT Health, Long School of Medicine, San Antonio, TX 78229, USA
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2021, 22(19), 10874; https://doi.org/10.3390/ijms221910874
Submission received: 31 August 2021 / Revised: 24 September 2021 / Accepted: 29 September 2021 / Published: 8 October 2021
(This article belongs to the Special Issue Melatonin: Molecular Mechanisms and Biological Functions. A 2021 Update)
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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.
Keywords: melatonin; cancer; antioxidant; apoptosis; angiogenesis; metastasis melatonin; cancer; antioxidant; apoptosis; angiogenesis; metastasis

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MDPI and ACS Style

Bastani, S.; Akbarzadeh, M.; Rastgar Rezaei, Y.; Farzane, A.; Nouri, M.; Mollapour Sisakht, M.; Fattahi, A.; Akbarzadeh, M.; Reiter, R.J. Melatonin as a Therapeutic Agent for the Inhibition of Hypoxia-Induced Tumor Progression: A Description of Possible Mechanisms Involved. Int. J. Mol. Sci. 2021, 22, 10874. https://doi.org/10.3390/ijms221910874

AMA Style

Bastani S, Akbarzadeh M, Rastgar Rezaei Y, Farzane A, Nouri M, Mollapour Sisakht M, Fattahi A, Akbarzadeh M, Reiter RJ. Melatonin as a Therapeutic Agent for the Inhibition of Hypoxia-Induced Tumor Progression: A Description of Possible Mechanisms Involved. International Journal of Molecular Sciences. 2021; 22(19):10874. https://doi.org/10.3390/ijms221910874

Chicago/Turabian Style

Bastani, Sepideh, Moloud Akbarzadeh, Yeganeh Rastgar Rezaei, Ali Farzane, Mohammad Nouri, Mahsa Mollapour Sisakht, Amir Fattahi, Maryam Akbarzadeh, and Russel J. Reiter. 2021. "Melatonin as a Therapeutic Agent for the Inhibition of Hypoxia-Induced Tumor Progression: A Description of Possible Mechanisms Involved" International Journal of Molecular Sciences 22, no. 19: 10874. https://doi.org/10.3390/ijms221910874

APA Style

Bastani, S., Akbarzadeh, M., Rastgar Rezaei, Y., Farzane, A., Nouri, M., Mollapour Sisakht, M., Fattahi, A., Akbarzadeh, M., & Reiter, R. J. (2021). Melatonin as a Therapeutic Agent for the Inhibition of Hypoxia-Induced Tumor Progression: A Description of Possible Mechanisms Involved. International Journal of Molecular Sciences, 22(19), 10874. https://doi.org/10.3390/ijms221910874

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