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Review
. 2017 Aug 9;8(52):90545-90556.
doi: 10.18632/oncotarget.20079. eCollection 2017 Oct 27.

Melatonin as a potential inhibitory agent in head and neck cancer

Chia-Ming Yeh #  1 , Shih-Chi Su #  2 , Chiao-Wen Lin  3   4 , Wei-En Yang  1   5 , Ming-Hsien Chien  6 , Russel J Reiter  7 , Shun-Fa Yang  1   5
Affiliations
Review

Melatonin as a potential inhibitory agent in head and neck cancer

Chia-Ming Yeh et al. Oncotarget. .

Abstract

Melatonin is a molecule secreted by the pineal gland; it is an important regulator of sleep and circadian rhythms. Through multiple interrelated mechanisms, melatonin exhibits various inhibitory properties at different stages of tumor progression. Many studies have explored the oncostatic effects of melatonin on hormone-dependent tumors. In this review, we highlight recent advances in understanding the effects of melatonin on the development of head and neck cancers, including molecular mechanisms identified through experimental and clinical observations. Because melatonin exerts a wide range of effects, melatonin may influence many mechanisms that influence the development of cancer. These include cell proliferation, apoptosis, angiogenesis, extracellular matrix remodeling through matrix metalloproteinases, and genetic polymorphism. Thus, the evidence discussed in this article will serve as a basis for basic and clinical research to promote the use of melatonin for understanding and controlling the development of head and neck cancers.

Keywords: head and neck cancers; matrix metalloproteinase; melatonin; metastasis.

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Conflict of interest statement

CONFLICTS OF INTEREST The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1. Effect of melatonin on the physiological and pathological functions
Melatonin regulates sleep and circadian rhythms. Moreover, melatonin also has anti-oxidant and anti-inflammation abilities to scavenge free radical and reduce the release of cytokines. Melatonin may reduce the development of cancer through affecting the mechanism of angiogenesis, metastasis and proliferation.
Figure 2
Figure 2. Proposed oncostatic actions of melatonin on head and neck cancer (HNSCC)
Melatonin treatment reduces HNSCC cell metastasis through inhibiting the expression of MMP-9 by targeting the ERK/JNK signal pathway to mediate histone acetylation and SP-1 expression. Melatonin inhibits HNSCC cell proliferation through upregulating p38, H2AX and p53 expression and downregulating the expression of hnRNPA1 and mir-24. Melatonin supplementation suppresses NHSCC cells angiogenesis by reducing the expression of angiogenesis molecular markers, HIF-1α and VEGF. ERK, mitogen-activated protein kinase; JNK, c-Jun N-terminal kinase; MMP-9, matrix metalloproteinase 9; H2AX, H2A histone family member X; hnRNPA1, heterogeneous nuclear ribonucleoprotein A1; HIF-1α, hypoxia inducible factor 1 alpha subunit; VEGF, vascular endothelial growth factor.
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