Holanda Isabel Cruz Luis

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, primarily driven by chronic inflammation from viral hepatitis, metabolic dysfunction, alcohol-induced liver disease, and cirrhosis. Conventional therapies often fail in advanced stages, highlighting the need for mechanism-based, precision-guided interventions. Plant-derived secondary metabolites represent a promising class of bioactive compounds with structural diversity, multitarget activity, anti-inflammatory effects, and favorable toxicity profiles. This review follows a semi-systematic narrative that synthesizes preclinical and experimental evidence on the anti-inflammatory and anticancer properties of key phytochemicals, including epigallocatechin-3-gallate, galangin, resveratrol, quercetin, curcumin, berberine, genistein, and thymoquinone. These compounds consistently modulate critical inflammation-driven signaling pathways, PI3K/AKT/mTOR, NF-κB, JAK/STAT, Wnt/β-catenin, and MAPK, resulting in apoptosis induction, cell cycle arrest, inhibition of angiogenesis, and reduced invasion and metastasis in multiple HCC models. Despite strong preclinical evidence, clinical translation remains limited by variable bioavailability, incomplete safety data, and insufficient human studies. A staged development strategy is recommended: standardized formulations, Good Laboratory Practice-compliant pharmacokinetic/toxicology studies, validation in patient-derived models, and early-phase, biomarker-guided clinical trials with combination therapy arms. Addressing regulatory, manufacturing, and quality control considerations will be essential for advancing these compounds as adjuvant or complementary agents in precision HCC therapy.

O-linked β-N-acetylglucosamine (O-GlcNAc, O-GlcNAcylation) is a post-translational modification of serine/threonine residues of proteins. Alterations in O-GlcNAcylation have been implicated in several types of cancer, regulation of tumor progression, inflammation, and thrombosis through its interaction with signaling pathways. We aim to explore the relationship between O-GlcNAcylation and hemostasis, inflammation, and cancer, which could serve as potential prognostic tools or clinical predictions for cancer patients’ healthcare and as an approach to combat cancer. We found that cancer is characterized by high glucose demand and consumption, a chronic inflammatory state, a state of hypercoagulability, and platelet hyperaggregability that favors thrombosis; the latter is a major cause of death in these patients. Furthermore, we review transcription factors and pathways associated with O-GlcNAcylation, thrombosis, inflammation, and cancer, such as the PI3K/Akt/c-Myc pathway, the nuclear factor kappa B pathway, and the PI3K/AKT/mTOR pathway. We also review infectious agents associated with cancer and chronic inflammation and potential inhibitors of cancer cell development. We conclude that it is necessary to approach both the diagnosis and treatment of cancer as a network in which multiple signaling pathways are integrated, and to search for a combination of potential drugs that regulate this signaling network.

La conjugación de nanoestructuras con moléculas bioactivas se emplea en el diagnósticos y tratamiento del cáncer. La quercetina (QUE) es un flavonoide con efecto antioxidante que inhibe el estrés oxidativo y la viabilidad de células cancerosas. Phaseolus lunatus (PHA) es una lectina con afinidad a estructuras de N-acetil-D-galactosamina (GalNAc) por lo cual aglutina eritrocitos del grupo sanguíneo A. El objetivo de este trabajo fue modelar la interacción entre QUE, PHA con nanotubos de carbono de pared múltiple carboxilados (NTCPM-co) mediante docking y dinámica molecular, utilizando HEX6.3 y AMBER22. Se identificaron seis sitios de interacción entre QUE y PHA (F12-V114-N129-D217-D218-W219), mientras que los NTCPM-co no interfieren con los sitios de reconocimiento a GalNAc de la lectina. En conclusión, la implementación de nanovectores acoplados a QUE y PHA podría mejorar el efecto citotóxico sobre células cancerígenas.