Melatonin as an Adjuvant to Antiangiogenic Cancer Treatments

SIMPLE SUMMARY: Chemo- and radiotherapy have an outstanding function in cancer treatment. In the last few years, in order to reduce the occurrence of adverse effects and to increase the efficacy of these treatments, there has been a growing interest in bringing together chemotherapeutic agents and ionizing radiation with other adjuvant therapies, antiangiogenic therapy being an example. Within the antitumor actions of melatonin is the inhibition of angiogenesis in diverse cancer types. In this review, we summarize present knowledge on the act of melatonin as a promising cancer cells sensitizer molecule to chemo- and radiotherapy through antiangiogenic actions. ABSTRACT: Melatonin is a hormone with different functions, antitumor actions being one of the most studied. Among its antitumor mechanisms is its ability to inhibit angiogenesis. Melatonin shows antiangiogenic effects in several types of tumors. Combination of melatonin and chemotherapeutic agents have a synergistic effect inhibiting angiogenesis. One of the undesirable effects of chemotherapy is the induction of pro-angiogenic factors, whilst the addition of melatonin is able to overcome these undesirable effects. This protective effect of the pineal hormone against angiogenesis might be one of the mechanisms underlying its anticancer effect, explaining, at least in part, why melatonin administration increases the sensitivity of tumors to the inhibitory effects exerted by ordinary chemotherapeutic agents. Melatonin has the ability to turn cancer totally resistant to chemotherapeutic agents into a more sensitive chemotherapy state. Definitely, melatonin regulates the expression and/or activity of many factors involved in angiogenesis which levels are affected (either positively or negatively) by chemotherapeutic agents. In addition, the pineal hormone has been proposed as a radiosensitizer, increasing the oncostatic effects of radiation on tumor cells. This review serves as a synopsis of the interaction between melatonin and angiogenesis, and we will outline some antiangiogenic mechanisms through which melatonin sensitizes cancer cells to treatments, such as radiotherapy or chemotherapy.