Melatonin and non-small cell lung cancer: new insights into signaling pathways

Abstract

Non-small-cell lung cancer (NSCLC) is a type of malignancy with progressive metastasis having poor prognosis and lowered survival resulting from late diagnosis. The therapeutic approaches for the treatment of this incurable cancer are chemo- and radiotherapy. Since current treatments are insufficient and because of drug-induced undesirable side effects and toxicities, alternate treatments are necessary and critical. The role of melatonin, produced in and released from the pineal gland, has been documented as a potential therapy for NSCLC. Melatonin prevents tumor metastasis via inducing apoptosis processes and restraining the autonomous cell proliferation. Moreover, melatonin inhibits the progression of tumors due to its oncostatic, pro-oxidant and anti-inflammatory effects. As a result, the combined treatment with melatonin and chemotherapy may have a synergistic effect, as with some other tumors, leading to a prolonged survival and improved quality of life in patients with NSCLC. This review summarizes the available data, based on the molecular mechanisms and related signaling pathways, to show how melatonin and its supplementation function in NSCLC.

Relationship between autophagy, apoptosis and endoplasmic reticulum stress induced by melatonin in osteoblasts by septin7 expression

“…apoptosis is a type of programmed cell death controlled by genes, including Bax and Bcl-2, that occurs as a homeostatic mechanism to maintain cell populations in the internal environment (11,29). Tumor cell studies have shown that melatonin can induce apoptosis (30); the present study demonstrated that early and late apoptotic rates of osteoblast cells treated with melatonin increased significantly as the concentration increased. The data also indicated that chromatin condensation in the nucleus and high expression of ParP-1 could be observed in osteoblast cells treated with 2 mM melatonin.…”

RAC1 Involves in the Radioresistance by Mediating Epithelial-Mesenchymal Transition in Lung Cancer

“…Medical treatments to cure NSCLC are mainly surgery, radiation therapy, and chemotherapy (3). Radiation therapy combined with chemotherapy can produce a cure only in a small number of NSCLC patients because NSCLC is comparatively less sensitive to chemotherapy or radiation (4,5). Acquired resistance results in local tumor recurrence or failure of radiotherapy (6,7).…”

Melatonin’s Antineoplastic Potential Against Glioblastoma

“…Mitochondria are the main source of reactive oxygen species (ROS) production and are a known target of melatonin [61,62]. As previously reported, melatonin presented a pro-oxidant effect in cancer cells [34][35][36]. A high concentration of ROS can damage mitochondrial and nuclear DNA and modify the expression of oncogenes and tumor suppressor genes [63,64].…”

“…The antioxidant activity of melatonin is observed through the prevention of free radical formation, as well as the capacity to upregulate antioxidant enzyme activity and downregulate pro-oxidant enzymes [31][32][33]. Furthermore, in cancer cells, melatonin presents a paradoxical pro-oxidant effect, leading to cell death [34][35][36]. Therefore, melatonin may inhibit cancer development by increasing the induction of oxidative stress in tumor cells [37].…”

“…Clinical and experimental studies showed that melatonin enhanced the antineoplastic activity of chemotherapy in various cancer types. This, along with significantly reducing chemotherapy side effects, improves the patient's quality of life [36,53,59]. McConnell et al [94] studied the effects of the association of melatonin to TMZ in cultured GBM cells and GSCs.…”