Due to its chemical properties and multiple molecular effects on different tumor cell types, the sesquiterpene lactone parthenolide (PN) can be considered an effective drug with significant potential in cancer therapy. PN has been shown to induce either classic apoptosis or alternative caspase-independent forms of cell death in many tumor models. The therapeutical potential of PN has been increased by chemical design and synthesis of more soluble analogues including dimethylaminoparthenolide (DMAPT). This review focuses on the molecular mechanisms of both PN and analogues action in tumor models, highlighting their effects on gene expression, signal transduction and execution of different types of cell death. Recent findings indicate that these compounds not only inhibit prosurvival transcriptional factors such as NF-κB and STATs but can also determine the activation of specific death pathways, increasing intracellular reactive oxygen species (ROS) production and modifications of Bcl-2 family members. An intriguing property of these compounds is its specific targeting of cancer stem cells. The unusual actions of PN and its analogues make these agents good candidates for molecular targeted cancer therapy.

Obesity is a complex disease caused by an excessive amount of body fat. Obesity is a medical problem and represents an important risk factor for the development of serious diseases such as insulin resistance, type 2 diabetes, cardiovascular disease, and some types of cancer. Not to be overlooked are the psychological issues that, in obese subjects, turn into very serious pathologies, such as depression, phobias, anxiety, and lack of self-esteem. In addition to modifying one’s lifestyle, the reduction of body mass can be promoted by different natural compounds such as essential oils (EOs). EOs are mixtures of aromatic substances produced by many plants, particularly in medicinal and aromatic ones. They are odorous and volatile and contain a mixture of terpenes, alcohols, aldehydes, ketones, and esters. Thanks to the characteristics of the various chemical components present in them, EOs are used in the food, cosmetic, and pharmaceutical fields. Indeed, it has been shown that EOs possess great antibiotic, anti-inflammatory, and antitumor powers. Emerging results also demonstrate the anti-obesity effects of EOs. We have examined the main data obtained in experimental studies and, in this review, we summarize the effect of EOs in obesity and obesity-related metabolic diseases.

Cow’s milk (CM) is a healthy food consumed worldwide by individuals of all ages. Unfortunately, “lactase-deficient” individuals cannot digest milk’s main carbohydrate, lactose, depriving themselves of highly beneficial milk proteins like casein, lactoalbumin, and lactoglobulin due to lactose intolerance (LI), while other individuals develop allergies specifically against these proteins (CMPA). The management of these conditions differs, and an inappropriate diagnosis or treatment may have significant implications for the patients, especially if they are infants or very young children, resulting in unnecessary dietary restrictions or avoidable adverse reactions. Omics technologies play a pivotal role in elucidating the intricate interactions between nutrients and the human body, spanning from genetic factors to the microbiota profile and metabolites. This comprehensive approach enables the precise delineation and identification of distinct cohorts of individuals with specific dietary requirements, so that tailored nutrition strategies can be developed. This is what is called personalized nutrition or precision nutrition (PN), the area of nutrition that focuses on the effects of nutrients on the genome, proteome, and metabolome, promoting well-being and health, preventing diseases, reducing chronic disease incidence, and increasing life expectancy. Here, we report the opinion of the scientific community proposing to replace the “one size fits all” approach with tailor-made nutrition programs, designed by integrating nutrigenomic data together with clinical parameters and microbiota profiles, taking into account the individual lactose tolerance threshold and needs in terms of specific nutrients intake. This customized approach could help LI patients to improve their quality of life, overcoming depression or anxiety often resulting from the individual perception of this condition as different from a normal state.

Several studies highlighted the beneficial value of natural compounds in the prevention and treatment of obesity. Here, we investigated the anti-obesity effects of extracts of peel and seed of mango (Mangifera indica L.) cultivated in Sicily (Italy) in 3T3-L1 cells. Mango Peel (MPE) and Mango Seed (MSE) extracts at a 100 µg/mL concentration significantly reduced lipid accumulation and triacylglycerol contents during 3T3-L1 adipocyte differentiation without toxicity. HPLC-ESI-MS analysis showed that both the extracts contain some polyphenolic compounds that can account for the observed biological effects. The anti-adipogenic effect of MPE and MSE was the result of down-regulation of the key adipogenic transcription factor PPARγ and its downstream targets FABP4/aP2, GLUT4 and Adipsin, as well SREBP-1c, a transcription factor which promotes lipogenesis. In addition, both MPE and MSE significantly activated AMPK with the consequent inhibition of Acetyl-CoA-carboxylase (ACC) and up-regulated PPARα. The addition of compound C, a specific AMPK inhibitor, reduced the effects of MPE and MSE on AMPK and ACC phosphorylation, suggesting a role of AMPK in mediating MPE and MSE anti-lipogenic effects. Notably, MPE and MSE possess an elevated radical scavenging activity, as demonstrated by DPPH radical scavenging assay, and reduced ROS content produced during adipocyte differentiation. This last effect could be a consequence of the increase in the antioxidant factors Nrf2, MnSOD and HO-1. In conclusion, MPE and MSE possesses both anti-adipogenic and antioxidant potential, thus suggesting that the bio-waste products of mango are promising anti-obesity natural compounds.

A diet rich in saturated fatty acids (FAs) has been correlated with metabolic dysfunction and ROS increase in the adipose tissue of obese subjects. Thus, reducing hypertrophy and oxidative stress in adipose tissue can represent a strategy to counteract obesity and obesity-related diseases. In this context, the present study showed how the peel and seed extracts of mango (Mangifera indica L.) reduced lipotoxicity induced by high doses of sodium palmitate (PA) in differentiated 3T3-L1 adipocytes. Mango peel (MPE) and mango seed (MSE) extracts significantly lowered PA-induced fat accumulation by reducing lipid droplet (LDs) and triacylglycerol (TAGs) content in adipocytes. We showed that MPE and MSE activated hormone-sensitive lipase, the key enzyme of TAG degradation. In addition, mango extracts down-regulated the adipogenic transcription factor PPARγ as well as activated AMPK with the consequent inhibition of acetyl-CoA-carboxylase (ACC). Notably, PA increased endoplasmic reticulum (ER) stress markers GRP78, PERK and CHOP, as well as enhanced the reactive oxygen species (ROS) content in adipocytes. These effects were accompanied by a reduction in cell viability and the induction of apoptosis. Interestingly, MPE and MSE counteracted PA-induced lipotoxicity by reducing ER stress markers and ROS production. In addition, MPE and MSE increased the level of the anti-oxidant transcription factor Nrf2 and its targets MnSOD and HO-1. Collectively, these results suggest that the intake of mango extract-enriched foods in association with a correct lifestyle could exert beneficial effects to counteract obesity.

Triple-Negative Breast Cancer (TNBC) is a particularly aggressive subtype among breast cancers (BCs), characterized by anoikis resistance, high invasiveness, and metastatic potential as well as Epithelial–Mesenchymal Transition (EMT) and stemness features. In the last few years, our research focused on the function of MCL1, an antiapoptotic protein frequently deregulated in TNBC. Here, we demonstrate that MCL1 inhibition by A-1210477, a specific BH3-mimetic, promotes anoikis/apoptosis in the MDA-MB-231 cell line, as shown via an increase in proapoptotic markers and caspase activation. Our evidence also shows A-1210477 effects on Focal Adhesions (FAs) impairing the integrin trim and survival signaling pathways, such as FAK, AKT, ERK, NF-κB, and GSK3β-inducing anoikis, thus suggesting a putative role of MCL1 in regulation of FA dynamics. Interestingly, in accordance with these results, we observed a reduction in migratory and invasiveness capabilities as confirmed by a decrease in metalloproteinases (MMPs) levels following A-1210477 treatment. Moreover, MCL1 inhibition promotes a reduction in EMT characteristics as demonstrated by the downregulation of Vimentin, MUC1, DNMT1, and a surprising re-expression of E-Cadherin, suggesting a possible mesenchymal-like phenotype reversion. In addition, we also observed the downregulation of stemness makers such as OCT3/4, SOX2, NANOG, as well as CD133, EpCAM, and CD49f. Our findings support the idea that MCL1 inhibition in MDA-MB-231 could be crucial to reduce anoikis resistance, aggressiveness, and metastatic potential and to minimize EMT and stemness features that distinguish TNBC.