Metabolomics profiling and chemoresistance mechanisms in ovarian cancer cell lines: Implications for targeting glutathione pathway.

Ovarian cancer presents a significant challenge due to its high rate of chemoresistance, which complicates the effectiveness of drug-response therapy. This study provides a comprehensive metabolomic analysis of ovarian cancer cell lines OVCAR-3 and SK-OV-3, characterizing their distinct metabolic landscapes. Metabolomics coupled with chemometric analysis enabled us to discriminate between the metabolic profiles of these two cell lines. The OVCAR-3 cells, which are sensitive to doxorubicin (DOX), exhibited a preference for biosynthetic pathways associated with cell proliferation. Conversely, DOX-resistant SK-OV-3 cells favored fatty acid oxidation for energy maintenance. Notably, a marked difference in glutathione (GSH) metabolism was observed between these cell lines. Our investigations further revealed that GSH depletion led to a profound change in drug sensitivity, inducing a shift from a cytostatic to a cytotoxic response. The results derived from this comprehensive metabolomic analysis offer potential targets for novel therapeutic strategies to overcome drug resistance. Our study suggests that targeting the GSH pathway could potentially enhance chemotherapy's efficacy in treating ovarian cancer.

Natural essential oils as a new therapeutic tool in colorectal cancer.

Colorectal cancer (CRC) is the third most revalent type of cancer in the world and the second most common cause of cancer death (about 1 million per year). Historically, natural compounds and their structural analogues have contributed to the development of new drugs useful in the treatment of various diseases, including cancer. Essential oils are natural odorous products made up of a complex mixture of low molecular weight compounds with recognized biological and pharmacological properties investigated also for the prevention and treatment of cancer. The aim of this paper is to highlight the possible role of essential oils in CRC, their composition and the preclinical studies involving them. It has been reviewed the preclinical pharmacological studies to determine the experimental models used and the anticancer potential mechanisms of action of natural essential oils in CRC. Searches were performed in the following databases PubMed/Medline, Web of science, TRIP database, Scopus, Google Scholar using appropriate MeSH terms. The results of analyzed studies showed that EOs exhibited a wide range of bioactive effects like cytotoxicity, antiproliferative, and antimetastatic effects on cancer cells through various mechanisms of action. This updated review provides a better quality of scientific evidence for the efficacy of EOs as chemotherapeutic/chemopreventive agents in CRC. Future translational clinical studies are needed to establish the effective dose in humans as well as the most suitable route of administration for maximum bioavailability and efficacy. Given the positive anticancer results obtained from preclinical pharmacological studies, EOs can be considered efficient complementary therapies in chemotherapy in CRC.

The effects of thymoquinone on pancreatic cancer: Evidence from preclinical studies.

Thymoquinone (TQ) is a secondary metabolite found in abundance in very few plant species including Nigella sativa L., Monarda fistulosa L., Thymus vulgaris L. and Satureja montana L. Preclinical pharmacological studies have shown that TQ has many biological activities, such as anti-inflammatory, antioxidant and anticancer. Both in vivo and in vitro experiments have shown that TQ acts as an antitumor agent by altering cell cycle progression, inhibiting cell proliferation, stimulating apoptosis, inhibiting angiogenesis, reducing metastasis and affecting autophagy. In this comprehensive study, the evidence on the pharmacological potential of TQ on pancreatic cancer is reviewed. The positive results of preclinical studies support the view that TQ can be considered as an additional therapeutic agent against pancreatic cancer. The possibilities of success for this compound in human medicine should be further explored through clinical trials.

Bioactive Compounds as Potential Agents for Sexually Transmitted Diseases Management: A Review to Explore Molecular Mechanisms of Action.

Sexually transmitted diseases (STDs) are produced by pathogens like bacteria, fungi, parasites, and viruses, and may generate severe health problems such as cancer, ulcers, and even problems in the newborn. This narrative review aims to present updated information about the use of natural bioactive compounds for the prevention and treatment of sexually transmitted infections. A search of the literature was performed using databases and search engines such as PubMed, Scopus, Google Scholar and Science Direct. From the pharmacotherapeutic management point of view, any strategies for prevention should contain medical approaches. The bioactive compounds obtained from natural products have shown biological effects against different microorganisms for the treatment of these diseases. The main results showed antimicrobial, antiprotozoal, antifungal and antiviral effects such as HIV. Also, the molecular mechanisms, signalling pathways and action targets of natural compounds were highlighted, thus justifying bacterial and antifungal inhibition, apoptosis or reduction of viral replication. From the data of our study, we can conclude that natural compounds may be a significant source for adjuvant drugs / complementary therapies in the treatment of STDs. With all these benefits, the future must conduct extensive clinical trials and the development of pharmaceutical nanotechnologies for a greater therapeutic effect.

Targeting Xanthine Oxidase by Natural Products as a Therapeutic Approach for Mental Disorders.

Mental disorders comprise diverse human pathologies, including depression, bipolar affective disorder, schizophrenia, and dementia that affect millions of people around the world. The causes of mental disorders are unclear, but growing evidence suggests that oxidative stress and the purine/adenosine system play a key role in their development and progression. Xanthine oxidase (XO) is a flavoprotein enzyme essential for the catalysis of the oxidative hydroxylation of purines -hypoxanthine and xanthine- to generate uric acid. As a consequence of the oxidative reaction of XO, reactive oxygen species (ROS) such as superoxide and hydrogen peroxide are produced and, further, contribute to the pathogenesis of mental disorders. Altered XO activity has been associated with free radical-mediated neurotoxicity inducing cell damage and inflammation. Diverse studies reported a direct association between an increased activity of XO and diverse mental diseases including depression or schizophrenia. Small-molecule inhibitors, such as the well-known allopurinol, and dietary flavonoids, can modulate the XO activity and subsequent ROS production. In the present work, we review the available literature on XO inhibition by small molecules and their potential therapeutic application in mental disorders. In addition, we discuss the chemistry and molecular mechanism of XO inhibitors, as well as the use of structure-based and computational methods to design specific inhibitors with the capability of modulating XO activity.