Quantitative Proteomic Profiling Reveals That Diverse Metabolic Pathways Are Influenced by Melatonin in an in Vivo Model of Ovarian Carcinoma

Abstract

To obtain more information into the molecular mechanisms underlying ovarian cancer (OC), we proposed a comparative proteomic analysis in animals receiving long-term melatonin as therapy or only vehicle using multidimensional protein identification combined with mass spectrometry. To induce tumor, a single dose of 100 μg 7,12-dimethylbenz(a)anthracene (DMBA) dissolved in 10 μL of sesame oil was injected under the left ovarian bursa of 20 Fischer 344 rats. The right ovaries were injected with sesame oil only. After tumors were developed, half of the animals received intraperitoneal administration of melatonin (200 μg/100g body weight/day) for 60 days. Melatonin therapy promoted down-regulation in numerous proteins involved in OC signaling pathways. The most significant portion of these proteins are involved in several metabolic processes, mainly those associated with mitochondrial systems, generation of metabolites and energy, hypoxia-inducible factor-1 signaling, antigen processing and presentation, endoplasmic reticulum stress-associated pathways, and cancer-related proteoglycans. A small number of proteins that were overexpressed by melatonin therapy included ATP synthase subunit β, fatty acid-binding protein, and 10-kDa heat shock protein. Taken together, our findings suggest that melatonin therapy efficiently modulated important signaling pathways involved in OC, and these proteins might be further targets that should be explored in new therapeutic opportunities for OC.

Melatonin, a Full Service Anti-Cancer Agent: Inhibition of Initiation, Progression and Metastasis

“…Subsequent studies confirmed that the molecular events normally associated with this type of experimental ovarian cancers were reversed by melatonin treatment [230,231,232]. Most recently, quantitative profiling of these tumors verified the broad modulatory actions of melatonin on essential signaling pathways in ovarian cancer cells [233] hinting at the possibility that melatonin should be considered as a therapeutic opportunity for women with this deadly disease. At the clinical level, melatonin has not been used as an adjuvant treatment for ovarian cancer.…”

Melatonin signaling in T cells: Functions and applications

“…Also, the cellular metabolic pathways have critical roles in shaping T‐cell development, homeostasis, activation/differentiation, and memory processes . Whether melatonin regulates the biology of T cells through cellular metabolism is of interest as melatonin influences the metabolism of treated subjects . Through modulation of T‐cell responses, melatonin has beneficial actions in various inflammatory diseases, such as T1D, SLE, and MS.…”

“…187 Whether melatonin regulates the biology of T cells through cellular metabolism is of interest as melatonin influences the metabolism of treated subjects. 188,189 Through modulation of T-cell responses, melatonin has beneficial actions in various inflammatory diseases, such as T1D, SLE, and MS. However, additional experiments are necessary before its clinical application as a therapeutic or adjuvant therapy can be initiated for treatment of these and other autoimmune diseases.…”

Melatonin Reduces Angiogenesis in Serous Papillary Ovarian Carcinoma of Ethanol-Preferring Rats

“…Moreover, acetaldehyde originating from ethanol oxidation acts as a co-carcinogenic agent through association with DNA, and by promoting cross-links between pairs of bases G:A and A:T [7,8]. Notably, we have developed a useful ethanol-preferring rat model that strictly reflects the aspects of serous papillary OC after chemical induction with a carcinogen [9,10]; this model provides an appropriate histological and molecular background that is needed to evaluate new chemoprotective compounds.…”