Molecular basis of melatonin protective effects in metastasis: A novel target of melatonin

Currently, cancer is ranked among the top ten causes of death worldwide. Despite the advances made in the field of cancer treatment, 5-year survival rates of various types of cancer are still low due to the recurrence of the disease and/or metastasis. Dissemination of cancer cells, infiltration into the blood vessels, migration to the targeted organs, extravasation, and colonization are the main steps of metastasis. Various factors and signaling pathways are involved in each of these steps. Melatonin (MLT) is a hormone derived from tryptophan and secreted by the pineal gland. This hormone has shown a variety of anti-tumor effects, including anti-oxidative activities, inhibiting the proliferation of tumor cells, inducing apoptosis, and suppressing metastasis. Due to these extensive effects, several studies have been conducted on the applications of MLT in treating different types of cancer. Herein, we review the mechanisms of MLT's effects on the metastasis inhibition of the most lethal types of cancer including the cancer of lung, breast, stomach, kidney, colon, liver, bladder, and pancreas. We discuss how MLT targets different molecules and signaling pathways in each step of the metastasis, such as angiogenesis, remodeling of the extracellular matrix, migration, and epithelial-to-mesenchymal transition.