Melatonin regulates endoplasmic reticulum stress in diverse pathophysiological contexts: A comprehensive mechanistic review.

The endoplasmic reticulum (ER) is crucial for protein quality control, and disruptions in its function can lead to various diseases. ER stress triggers an adaptive response called the unfolded protein response (UPR), which can either restore cellular homeostasis or induce cell death. Melatonin, a safe and multifunctional compound, shows promise in controlling ER stress and could be a valuable therapeutic agent for managing the UPR.

Melatonin changes energy metabolism and reduces oncogenic signaling in ovarian cancer cells.

Ovarian cancer (OC) adjusts energy metabolism in favor of its progression and dissemination. Because melatonin (Mel) has antitumor actions, we investigated its impact on energy metabolism and kinase signaling in OC cells (SKOV-3 and CAISMOV-24). Cells were divided into control and Mel-treated groups, in the presence or absence of the antagonist luzindole.

Melatonin Reverses the Warburg-Type Metabolism and Reduces Mitochondrial Membrane Potential of Ovarian Cancer Cells Independent of MT1 Receptor Activation.

Ovarian cancer (OC) is the most lethal gynecologic malignancy, and melatonin has shown various antitumor properties. Herein, we investigated the influence of melatonin therapy on energy metabolism and mitochondrial integrity in SKOV-3 cells and tested whether its effects depended on MT1 receptor activation. SKOV-3 cells were exposed to different melatonin concentrations, and experimental groups were divided as to the presence of MT1 receptors (melatonin groups) or receptor absence by RNAi silencing (siRNA MT1+melatonin).

The proteomic landscape of ovarian cancer cells in response to melatonin.

Ovarian cancer (OC) is the most lethal gynecological malignancy with a highly negative prognosis. Melatonin is an indoleamine secreted by the pineal gland during darkness and has shown antitumor activity in both in vitro and in vivo experiments. Herein, we investigated the influence of melatonin on the proteome of human ovarian carcinoma cells (SKOV-3 cell line) using the Ultimate 3000 LC Liquid NanoChromatography equipment coupled to a Q-Exactive mass spectrometry.

Protein restriction during puberty alters nutritional parameters and affects ovarian and uterine histomorphometry in adulthood in rats.

In a large part of the population inefficient ingestion of proteins, whether for cultural, aesthetic or economic reasons, is a global concern. Low-protein diets can cause severe functional complications, mainly during the development and maturation of organs and systems, including the female reproductive system. The present study investigated the effect of nutritional protein restriction during puberty on the oestrous cycle and expression of sex steroid receptors (AR, ERα e ERβ) in ovarian and uterine tissues of adult rats.

Maternal protein restriction impairs nutrition and ovarian histomorphometry without changing p38MAPK and PI3K-AKT-mTOR signaling in adult rat ovaries.

Aims: Because an adequate protein supply is detrimental for the maintenance of folliculogenesis and ovulation, we evaluated the impact of maternal low protein diet on nutritional parameters, estrous cycle, ovarian histomorphometry, and on the expression of metabolic and survival signaling molecules in different follicular stages.

Main Methods: Twenty Wistar pregnant rats were divided into two groups: the normoprotein (NP) group, composed of animals that received 17% protein, and a low-protein (LP) group, composed of animals that received 6% protein during gestation and lactation period. After weaning, female rats were fed with standard diet until the 120-days-old.

P-MAPA activates TLR2 and TLR4 signaling while its combination with IL-12 stimulates CD4+ and CD8+ effector T cells in ovarian cancer.

Aims: Ovarian cancer (OC) is the most lethal gynecological malignancies and many women develop chemoresistance associated with the inflammatory process. We investigated the effects of P-MAPA and IL-12 on the inflammatory and immune responses in a chemically-induced OC model.

Main Methods: OCs were induced with 7,12-dimethylbenz(a)anthracene into the ovarian bursa, and the animals were given P-MAPA (5 mg/kg bw.

The role of Toll-like receptor 4 signaling pathway in ovarian, cervical, and endometrial cancers.

Toll-like receptors (TLRs) are critical sensors related to inflammation and tumorigenesis. Among all subtypes, the TLR4 is a highly described transmembrane protein involved in the inflammatory process. The TLR4/myeloid differentiation factor 88 (MyD88) signaling pathway has been implicated in oncogenic events in several tissues and is associated with survival of patients.

Melatonin Promotes Uterine and Placental Health: Potential Molecular Mechanisms.

The development of the endometrium is a cyclic event tightly regulated by hormones and growth factors to coordinate the menstrual cycle while promoting a suitable microenvironment for embryo implantation during the "receptivity window". Many women experience uterine failures that hamper the success of conception, such as endometrium thickness, endometriosis, luteal phase defects, endometrial polyps, adenomyosis, viral infection, and even endometrial cancer; most of these disturbances involve changes in endocrine components or cell damage. The emerging evidence has proven that circadian rhythm deregulation followed by low circulating melatonin is associated with low implantation rates and difficulties to maintain pregnancy.

P-MAPA and IL-12 Differentially Regulate Proteins Associated with Ovarian Cancer Progression: A Proteomic Study.

To investigate the potential role of immunotherapies in the cellular and molecular mechanisms associated with ovarian cancer (OC), we applied a comparative proteomic toll using protein identification combined with mass spectrometry. Herein, the effects of the protein aggregate magnesium-ammonium phospholinoleate-palmitoleate anhydride, known as P-MAPA, and the human recombinant interleukin-12 (hrIL-12) were tested alone or in combination in human SKOV-3 cells. The doses and period were defined based on a previous study, which showed that 25 μg/mL P-MAPA and 1 ng/mL IL-12 are sufficient to reduce cell metabolism after 48 h.

Mitochondrial functions and melatonin: a tour of the reproductive cancers.

Cancers of the reproductive organs have a strong association with mitochondrial defects, and a deeper understanding of the role of this organelle in preneoplastic-neoplastic changes is important to determine the appropriate therapeutic intervention. Mitochondria are involved in events during cancer development, including metabolic and oxidative status, acquisition of metastatic potential, resistance to chemotherapy, apoptosis, and others. Because of their origin from melatonin-producing bacteria, mitochondria are speculated to produce melatonin and its derivatives at high levels; in addition, exogenously administered melatonin accumulates in the mitochondria against a concentration gradient.