In spite of major advances in oncology, the World Health Organization predicts that cancer incidence will double within the next two decades. Although it is well understood that cancer is a hyperproliferative disorder mediated through dysregulation of multiple cell signaling pathways, most cancer drug development remains focused on modulation of specific targets, mostly one at a time, with agents referred to as "targeted therapies," "smart drugs," or "magic bullets." How many cancer targets there are is not known, and how many targets must be attacked to control cancer growth is not well understood. Although more than 90% of cancer-linked deaths are due to metastasis of the tumor to vital organs, most drug targeting is focused on killing the primary tumor. Besides lacking specificity, the targeted drugs induce toxicity and side effects that sometimes are greater problems than the disease itself. Furthermore, the cost of some of these drugs is so high that most people cannot afford them. The present report describes the potential anticancer properties of curcumin, a component of the Indian spice turmeric (Curcuma longa), known for its safety and low cost. Curcumin can selectively modulate multiple cell signaling pathways linked to inflammation and to survival, growth, invasion, angiogenesis, and metastasis of cancer cells. More clinical trials of curcumin are needed to prove its usefulness in the cancer setting.
Diabetic neuropathy (DN) is a condition in which nerve fibers are continually exposed to high glucose-induced free radicals. Recent discoveries demonstrated that melatonin is an indole hormone that contributes to neuroprotection through the modulation of autophagy. Herein, this study aims to examine the neuroprotective effects of melatonin on Schwann cells under high glucose conditions. 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay was used to measure cell viability. The activation of autophagosomes was determined using acridine orange staining (AO). Western blot assay was used to measure the expression of proteins involved in autophagy and endoplasmic reticulum (ER) stress. Our results demonstrated that melatonin at 1 µM has the highest protective effects on high glucose-induced cell death. Melatonin concentrations of 5 and 10 µM were found to be the most effective in reducing autophagy induced by high glucose. Under high glucose conditions, the protein expressions of LC3, ATF4, ATF6, CHOP, PERK and eIF2-α were up-regulated in Schwann cells. However, melatonin attenuated these changes by downregulating LC3 and the ER stress markers ATF4, ATF6, CHOP, PERK and eIF2-α protein expressions in Schwann cells. In conclusion, melatonin alleviates high glucose-induced autophagy in Schwann cells through PERK-eIF2α-ATF4-CHOP signaling pathways.