What is known about melatonin, chemotherapy and altered gene expression in breast cancer

Abstract

Melatonin, synthesized in and released from the pineal gland, has been demonstrated by multiple in vivo and in vitro studies to have an oncostatic role in hormone-dependent tumors. Furthermore, several clinical trials point to melatonin as a promising adjuvant molecule to be considered for cancer treatment. In the past few years, evidence of a broader spectrum of action of melatonin as an antitumor agent has arisen; thus, melatonin appears to also have therapeutic effects in several types of hormone-independent cancer, including ovarian, leukemic, pancreatic, gastric and non-small cell lung carcinoma. In the present study, the latest findings regarding melatonin molecular actions when concomitantly administered with either radiotherapy or chemotherapy in cancer were reviewed, with a particular focus on hormone-dependent breast cancer. Finally, the present study discusses which direction should be followed in the next years to definitely clarify whether or not melatonin administration could protect against non-desirable effects (such as altered gene expression and post-translational protein modifications) caused by chemotherapy or radiotherapy treatments. As treatments move towards personalized medicine, comparative gene expression profiling with and without melatonin may be a powerful tool to better understand the antitumor effects of melatonin, the pineal gland hormone.

Usefulness of melatonin as complementary to chemotherapeutic agents at different stages of the angiogenic process

“…Combined with classical chemotherapeutic agents, melatonin enhances the efficacy of these drugs in breast cancer patients via a variety of mechanisms, including the capability of impairing angiogenesis 21,22,27,34 . Thus, in www.nature.com/scientificreports www.nature.com/scientificreports/ the present study, we analysed the effects of docetaxel and vinorelbine at different stages of angiogenesis, comparing the efficacy of the drugs alone or added together with the pineal hormone.…”

Melatonin enhances the apoptotic effects and modulates the changes in gene expression induced by docetaxel in MCF‑7 human breast cancer cells

“…The identification of such alterations may contribute to an improved efficacy and may help to elucidate the mechanisms responsible for undesirable processes, such as drug resistance. Gene expression and post-translational modification profiles have recently been obtained in all types of tumors and cancer cell lines treated with chemotherapeutic drugs (25,40).…”

“…Melatonin exerts anticancer effects at different phases of carcinogenesis, namely initiation, progression and spreading from the primary tumor (24). Recently, studies have addressed the potential benefits that melatonin could have on the effects of chemotherapeutic agents (25). The disruption of the nocturnal melatonin rhythm contributes to a complete loss of tumor sensitivity to doxorubicin (26), whereas melatonin co-treatment sensitizes cancer cells to this drug, increasing doxorubicin intracellular concentrations, possibly through a downregulation in the levels of P-glycoprotein (27).…”

The Roles of the Bone Marrow Microenvironment in Controlling Tumor Dormancy

“…217,229,236 Recently, a review of the effects of melatonin and chemotherapeutic agents in combination in cancer treatments has been published. 237 Although the information available is limited, the results obtained suggest that melatonin sensitizes tumor cells to the cytotoxic effects of chemotherapeutic agents.…”