The inhibitory effect of melatonin on human prostate cancer

Abstract

Prostate cancer (PCa) is one of the most commonly diagnosed human cancers in males. Nearly 191,930 new cases and 33,330 new deaths of PCa are estimated in 2020. Androgen and androgen receptor pathways played essential roles in the pathogenesis of PCa. Androgen depletion therapy is the most used therapies for primary PCa patients. However, due to the high relapse and mortality of PCa, developing novel noninvasive therapies have become the focus of research. Melatonin is an indole-like neurohormone mainly produced in the human pineal gland with a prominent anti-oxidant property. The anti-tumor ability of melatonin has been substantially confirmed and several related articles have also reported the inhibitory effect of melatonin on PCa, while reviews of this inhibitory effect of melatonin on PCa in recent 10 years are absent. Therefore, we systematically discuss the relationship between melatonin disruption and the risk of PCa, the mechanism of how melatonin inhibited PCa, and the synergistic benefits of melatonin and other drugs to summarize current understandings about the function of melatonin in suppressing human prostate cancer. We also raise several unsolved issues that need to be resolved to translate currently non-clinical trials of melatonin for clinic use. We hope this literature review could provide a solid theoretical basis for the future utilization of melatonin in preventing, diagnosing and treating human prostate cancer.

Metabolic Anti-Cancer Effects of Melatonin: Clinically Relevant Prospects

“…The imminent need to identify and investigate novel therapeutic approaches in cancer research determines melatonin as a promising agent targeted on cancer combined with conventional therapies. Further investigation on melatonin’s role in cancer initiation and progression can improve its therapeutical potential in the clinical sphere [ 102 , 163 , 164 , 165 ].…”

A Longitudinal Study of the Relationship between Shift Work and Prostate-Specific Antigen in Healthy Male Workers

“…Razavi et al also explained that a worse alignment of shift schedule and chronotype may disrupt the melatonin rhythms of the sleep–wake period [ 41 ]. In addition, Xi et al reported that melatonin may suppress the prostate cancer cell (LNCaP cell) through the melatonin receptor (MT1 receptor) with attenuated calcium influx, which activates protein kinase C to inhibit the PSA gene (KLK3 gene), consequently decreasing PSA levels [ 42 , 43 ]. From this point of view, it seems reasonable that a lack of melatonin results in increased PSA levels.…”

Membrane Melatonin Receptors Activated Cell Signaling in Physiology and Disease

“…Moreover, melatonin might impair the interrelations between the NF-κB and androgen receptor splice variant 7, thus detaining the development of resistance to androgen depletion therapy in advanced prostate cancer [ 309 ]. The oncostatic effects of melatonin include also induction of apoptosis, modulation of prostate tumor metabolism, decreased angiogenesis, and regulation of neuroendocrine differentiation, suppression of sirtuin-1 and local growth factors as well as amplification of cytokine-induced toxicity [ 290 , 310 ].…”