Cancer is a significant global public health issue and, despite advancements in detection and treatment, the prognosis remains poor. Cancer is a complex disease characterized by various hallmarks, including dysregulation in apoptotic cell death pathways. Apoptosis is a programmed cell death process that efficiently eliminates damaged cells. Several studies have indicated the involvement of polyunsaturated fatty acids (PUFAs) in apoptosis, including omega-3 PUFAs such as alpha-linolenic acid, docosahexaenoic acid, and eicosapentaenoic acid. However, the role of omega-6 PUFAs, such as linoleic acid, gamma-linolenic acid, and arachidonic acid, in apoptosis is controversial, with some studies supporting their activation of apoptosis and others suggesting inhibition. These PUFAs are essential fatty acids, and Western populations today have a high consumption rate of omega-6 to omega-3 PUFAs. This review focuses on presenting the diverse molecular mechanisms evidence in both in vitro and in vivo models, to help clarify the controversial involvement of omega-3 and omega-6 PUFAs in apoptosis mechanisms in cancer.

Natural biopolymer scaffolds and conductive nanomaterials have been widely used in cardiac tissue engineering; however, there are still challenges in the scaffold fabrication, which include enhancing nutrient delivery, biocompatibility and properties that favor the growth, maturation and functionality of the generated tissue for therapeutic application. In the present work, different scaffolds prepared with sodium alginate and chitosan (alginate/chitosan) were fabricated with and without the addition of metal nanoparticles and how their fabrication affects cardiomyocyte growth was evaluated. The scaffolds (hydrogels) were dried by freeze drying using calcium gluconate as a crosslinking agent, and two types of metal nanoparticles were incorporated, gold (AuNp) and gold plus sodium alginate (AuNp+Alg). A physicochemical characterization of the scaffolds was carried out by swelling, degradation, permeability and infrared spectroscopy studies. The results show that the scaffolds obtained were highly porous (>90%) and hydrophilic, with swelling percentages of around 3000% and permeability of the order of 1 × 10⁻⁸ m². In addition, the scaffolds proposed favored adhesion and spheroid formation, with cardiac markers expression such as tropomyosin, troponin I and cardiac myosin. The incorporation of AuNp+Alg increased cardiac protein expression and cell proliferation, thus demonstrating their potential use in cardiac tissue engineering.

Omega-3 polyunsaturated fatty acid (ω-3 PUFA) supplements for chemoprevention of different types of cancer including lung cancer has been investigated in recent years. ω-3 PUFAs are considered immunonutrients, commonly used in the nutritional therapy of cancer patients. ω-3 PUFAs play essential roles in cell signaling and in cell structure and fluidity of membranes. They participate in the resolution of inflammation and have anti-inflammatory effects. Lung cancer patients suffer complications, such as anorexia-cachexia syndrome, pain and depression. The European Society for Clinical Nutrition and Metabolism (ESPEN) 2017 guidelines for cancer patients only discuss the use of ω-3 PUFAs for cancer-cachexia treatment, leaving aside other cancer-related complications that could potentially be managed by ω-3 PUFAs. This review aims to elucidate whether the effects of ω-3 PUFAs in lung cancer is supplementary, pharmacological or both. In addition, clinical studies, evidence in cell lines and animal models suggest how ω-3 PUFAs induce anticancer effects. ω-3 PUFAs and their metabolites are suggested to modulate pivotal pathways underlying the progression or complications of lung cancer, indicating that this is a promising field to be explored. Further investigation is still required to analyze the benefits of ω-3 PUFAs as supplementation or pharmacological treatment in lung cancer.

Non-Hodgkin lymphoma (NHL) is one of the most common cancers in childhood. The development of chemoresistance in tumor cells is one of the principal causes of treatment failure. This resistance has been associated with different mechanisms, one being the overexpression of anti-apoptotic proteins such as Bcl-_xL. It has been shown that this protein is regulated by the transcription factor hypoxia inducible factor-1α (HIF-1α), which is overexpressed in several tumors including NHL, and the overexpression of both proteins may result in resistance to chemotherapy. We investigated the role of HIF-1α in resistance to chemotherapy via the induction of Bcl-_xL expression in NHL cell lines, using a pharmacological modulation of HIF-1α. Our data showed that treating Ramos cells with ethyl 3,4-dihydroxybenzoate, an inhibitor of prolyl hydroxylase, induces accumulation of HIF-1α and this correlates with an increase of Bcl-_xL as well as resistance to apoptosis after exposure to chemotherapeutics drugs. In contrast, the treatment of Ramos cells with 2-methoxyestradiol, an inhibitor of HIF-1α activity, induced down-regulation of Bcl-_xL expression, and this correlated with the sensitization of tumor cells to chemotherapeutic drugs. These data demonstrate that up-regulation of the anti-apoptotic protein Bcl-_xL in NHL cells correlates with HIF-1α expression and activity, through which a phenotype of chemoresistance is induced.

Resistance to chemotherapy hinders the successful treatment of acute lymphoblastic leukemia (ALL). The multi-drug resistance-1 (MDR1/ABCB1) gene encodes P‐glycoprotein (P-gp), which plays an important role in chemoresistance; however, its transcriptional regulation remains unclear. We investigated the role of YY1 in the regulation of MDR1 and its relation to ALL outcomes. Analysis of the MDR1 promoter revealed four putative YY1-binding sites, which we analyzed using a reporter system and ChIP analysis. YY1 silencing resulted in the inhibition of MDR1 expression and function. The clinical roles of YY1 and MDR1 expression were evaluated in children with ALL. Expression of both proteins was increased in ALL patients compared to controls. We identified a positive correlation between YY1 and MDR1 expression. High levels of YY1 were associated with decreased overall survival. Our results demonstrated that YY1 regulates the transcription of MDR1. Therefore, YY1 may serve as a useful prognostic and/or therapeutic target.

Aim: Investigate the role of hypoxia-inducible factor-1α (HIF-1α) in pulmonary tuberculosis (TB). Methods & results: A model of progressive pulmonary TB in BALB/c mice, immunohistochemistry and digital pathology were used. High HIF-1α expression was observed during early TB in activated macrophages. During late TB, even higher HIF-1α expression was observed in foamy macrophages, which are resistant to apoptosis. Blocking HIF-1α during early infection with 2-methoxyestradiol worsened the disease, while during late TB, it induced macrophage apoptosis and decreased bacillary loads. Conclusion: HIF-1α has a dual role in experimental TB. This finding could have therapeutic implications because combined treatment with 2-methoxyestradiol and antibiotics appeared to eliminate mycobacteria more efficiently than conventional chemotherapy during advanced disease.