The main treatment alternative for cervical cancer is cisplatin chemotherapy. However, the resistance of tumor cells to cisplatin, in addition to side effects, limits its use. The flavonoid naringenin has shown cytotoxic effects on tumor cells and may be considered as a coadjuvant in the treatment of cervical cancer. In the present study, the effect of naringenin on cell viability, cytotoxicity, proliferation, apoptosis and invasion was evaluated in HeLa spheroid cultures. Naringenin impaired the cell viability as indicated by low ATP levels and caused concentration- and time-dependent cytotoxicity via the loss of cell membrane integrity. Furthermore, it did not activate caspases 3, 7, 8, and 9, suggesting that the cytotoxic effect was by necrotic cell death instead of apoptosis. Additionally, proliferation in the G0/G1 phase of the cell cycle was inhibited. Cell invasion also decreased as time progressed. Later, we determined if naringenin could improve the anti-tumor effect of cisplatin. The combination of naringenin with low concentrations of cisplatin improved the effect of the drug by significantly decreasing cell viability, potentiating the induction of cytotoxicity and decreasing the invasive capacity of the spheroids. Since these effects are regulated by some key proteins, molecular docking results indicated the interaction of naringenin with RIP3 and MLKL, cyclin B and with matrix metalloproteases 2 and 9. The results showed the anti-tumor effect of naringenin on the HeLa spheroids and improved effect of the cisplatin at low concentrations in combination with naringenin, placing flavonoids as a potential adjuvant in the therapy against cervical cancer.

Obesity is an abnormal or excessive accumulation of fat that leads to different health problems, such as cancer, where the adipocytes promote the proliferation, migration, and invasion of cancer cells, especially in the breast, where the epithelial cells are immersed in a fatty environment, and the interactions between these two types of cells involve, not only adipokines but also local pro-inflammatory mechanisms and hypoxic processes generating anti-apoptotic signals, which are a common result in leptin signaling. The expression of the Vascular Endothelial Growth Factor (VEGF) and cyclin D1, results in the decrease in phosphorylation of AMPK, increasing the activity of the aromatase enzyme; alternatively, the adiponectin activates AMPK to reduce inflammation. Nevertheless, alterations of the JAK/STAT pathways contribute to mammary carcinogenesis, while the PI3K/AKT/mTOR pathway controls most of the cancer’s characteristics such as the cell cycle, survival, differentiation, proliferation, motility, metabolism, and genetic stability. Therefore, the purpose of the present review is, through the accumulated scientific evidence, to find the concordance between the signaling pathways involved among obesity and breast cancer, which can be modulated by using flavonoids.

Echinacea spp. displays different biological activities, such as antiviral, immunomodulatory, and anticancer activities. Currently, high sales of hydroalcoholic extracts of Echinacea have been repo...

Cancer is a disease with the highest mortality and morbidity rate worldwide. First-line drugs induce several side effects that drastically reduce the quality of life of people with this disease. Finding molecules to prevent it or generate less aggressiveness or no side effects is significant to counteract this problem. Therefore, this work searched for bioactive compounds of marine macroalgae as an alternative treatment. An 80% ethanol extract of dried Caulerpa sertularioides (CSE) was analyzed by HPLS-MS to identify the chemical components. CSE was utilized through a comparative 2D versus 3D culture model. Cisplatin (Cis) was used as a standard drug. The effects on cell viability, apoptosis, cell cycle, and tumor invasion were evaluated. The IC₅₀ of CSE for the 2D model was 80.28 μg/mL versus 530 μg/mL for the 3D model after 24 h of treatment exposure. These results confirmed that the 3D model is more resistant to treatments and complex than the 2D model. CSE generated a loss of mitochondrial membrane potential, induced apoptosis by extrinsic and intrinsic pathways, upregulated caspases-3 and -7, and significantly decreased tumor invasion of a 3D SKLU-1 lung adenocarcinoma cell line. CSE generates biochemical and morphological changes in the plasma membrane and causes cell cycle arrest at the S and G2/M phases. These findings conclude that C. sertularioides is a potential candidate for alternative treatment against lung cancer. This work reinforced the use of complex models for drug screening and suggested using CSE’s primary component, caulerpin, to determine its effect and mechanism of action on SKLU-1 in the future. A multi-approach with molecular and histological analysis and combination with first-line drugs must be included.

Quorum sensing (QS) is a bacterial cell communication system in Pseudomonas aeruginosa , which regulates the production of several virulence factors, including pyocyanin, exoproteases, and biofilm formation. Natural products (NPs) have demonstrated their ability to control QS in different bacteria. This work evaluated the antimicrobial and anti‐QS potential of a small library of NPs from Mexican biodiversity against P. aeruginosa PA14. Alternariol 4‐methyl ether ( 12 ), iridoskyrin ( 17 ), and 5,8‐epi‐dioxyergosta‐6,9(11),22‐trien‐3‐ol ( 39 ) showed the most potent antimicrobial activity at both test concentrations. Regarding anti‐QS activity, fuscin ( 13 ), neosartorin ( 18 ), 8ʹ‐hydroxy zearalenone ( 21 ), penicillic acid ( 26 ), 5,6‐dehydroxypenicillic acid ( 27 ), pitholide B ( 36 ), and citrinin ( 38 ) inhibited pyocyanin production, exoproteases activity, and biofilm formation at the lowest concentration without significantly altering growth. Subsequently, in silico studies of deep‐learning molecular docking and molecular dynamics indicated the putative mechanism of action of these compounds through their binding to the ligand‐binding domains of LasR and RhlR, target proteins that control QS systems. These results demonstrate that NPs, such as pitholide B ( 36 ) and citrinin ( 38 ), are potential candidates against P. aeruginosa .