Promising Antineoplastic Actions of Melatonin

Abstract

Melatonin is an endogenous indoleamine with an incredible variety of properties and activities. In recent years, an increasing number of studies have investigated this indoleamine's interaction with cancerous cells. In particular, it seems that melatonin not only has the ability to improve the efficacy of many drugs used in chemotherapy but also has a direct inhibitory action on neoplastic cells. Many publications underlined the ability of melatonin to suppress the proliferation of various cancer cells or to modulate the expression of membrane receptors on these cells, thereby reducing tumor aggressiveness to metastasize. In addition, while melatonin has antiapoptotic actions in normal cells, in many cancer cells it has proapoptotic effects; these dichotomous actions have gained the interest of researchers. The increasing focus on melatonin in the field of oncology and the growing number of studies on this topic require a deep understanding of what we already know about the antineoplastic actions of melatonin. This information would be of value for potential use of melatonin against neoplastic diseases.

Keywords: apoptosis; cancer hallmarks; cancer treatment; melatonin; oncology.

FIGURE 1

Schematic representation of cancer hallmarks with the indication of the main markers involved in the corresponding hallmark. FGFR, fibroblast growth factor receptor; HER2, human epidermal growth factor receptor 2; PKM, pyruvate kinase M; VEGF, vascular endothelial growth factor.

FIGURE 2

Schematic representation of the extrinsic and intrinsic pathways of apoptosis. APAF 1, apoptotic protease-activating factor 1; DD, death domain; DED, death effector domain; FADD, Fas-associated protein with death domain; TNFRSF, tumor necrosis factor receptor superfamily.

FIGURE 3

Schematic representation of melatonin’s inhibition of cancer hallmarks with an indication of the main target molecules and the corresponding hallmark.

FIGURE 4

Schematic representation of the main interaction of melatonin in the pathways of apoptosis. APAF 1, apoptotic protease-activating factor 1; DD, death domain; DED, death effector domain; FADD, Fas-associated protein with death domain; TNFRSF, tumor necrosis factor receptor superfamily.