Significance of flavonoids targeting PI3K/Akt/HIF-1α signaling pathway in therapy-resistant cancer cells – A potential contribution to the predictive, preventive, and personalized medicine

Journal of Advanced Research, Год журнала: 2023, Номер 55, С. 103 - 118

Опубликована: Март 4, 2023

Cancer management faces multiple obstacles, including resistance to current therapeutic approaches. In the face of challenging microenvironments, cancer cells adapt metabolically maintain their supply energy and precursor molecules for biosynthesis thus sustain rapid proliferation tumor growth. Among various metabolic adaptations observed in cells, altered glucose metabolism is most widely studied. The aberrant glycolytic modification has been associated with cell division, growth, progression, drug resistance. higher rates glycolysis as a hallmark modulated by transcription factor hypoxia inducible 1 alpha (HIF-1α), downstream target PI3K/Akt signaling, deregulated pathway cancer. We provide detailed overview current, primarily experimental, evidence on potential effectiveness flavonoids combat glycolysis-induced conventional targeted therapies. manuscript focuses reducing via affecting PI3K/Akt, HIF-1α (as critical that regulated pathway), key mediators PI3K/Akt/HIF-1α signaling (glucose transporters enzymes). working hypothesis proposes – an attractive application mitigate Phytochemicals represent source promising substances applicable primary, secondary, tertiary care. However, accurate patient stratification individualized profiling crucial steps paradigm shift from reactive predictive, preventive, personalized medicine (PPPM / 3PM). article focused targeting molecular patterns natural provides evidence-based recommendations 3PM relevant implementation.

Язык: Английский

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Current Advances in the Therapeutic Potential of Scutellarin: Novel Applications, Mechanisms, and Future Challenges.

Phytomedicine Plus, Год журнала: 2025, Номер unknown, С. 100754 - 100754

Опубликована: Янв. 1, 2025

Язык: Английский

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Phytoflavonoids as alternative therapeutic effect for melanoma: Integrative Network pharmacology, molecular dynamics and drug-likeness profiling for lead discovery

Computational Biology and Chemistry, Год журнала: 2025, Номер 117, С. 108390 - 108390

Опубликована: Фев. 22, 2025

Язык: Английский

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Targeting the MAPK signaling pathway: implications and prospects of flavonoids in 3P medicine as modulators of cancer cell plasticity and therapeutic resistance in breast cancer patients

The EPMA Journal, Год журнала: 2025, Номер unknown

Опубликована: Апрель 10, 2025

Cancer drug resistance poses a significant challenge in oncology, primarily driven by cancer cell plasticity, which promotes tumor initiation, progression, metastasis, and therapeutic evasion many different cancers. Breast cancers (BCs) are prominent example of that, with an estimated 2.3 million new cases 670,000 BC-related deaths registered worldwide annually. Triple-negative BC is especially challenging for treatments demonstrating particularly aggressive disease course, early manifestation metastatic disease, frequent drug-resistant types, poor individual outcomes. Although chemosensitizing agents have been developed, their clinical utility oncology remains unproven. The mitogen-activated protein kinase (MAPK) pathway considered critical regulator intracellular extracellular signaling highly relevant both - genetic epigenetic modifications. Dysregulation the MAPK pathways plays role conferring chemoresistance BC. Contextually, targeting represents promising strategy overcoming enhancing efficacy anticancer treatment. On other hand, flavonoids, class phytochemicals, key modulators signaling. Flavonoids interact ERK, JNK, p38, ERK5 cascade present avenue developing novel anti-cancer therapies re-sensitizing treatment Compounds such as quercetin, kaempferol, genistein, luteolin, myricetin, EGCG, baicalein, baicalin, nobiletin, morin, delphinidin, acacetin, isorhamnetin, apigenin, silymarin, among others, identified specific signaling, exerting complex downstream effects cells increasing therewith suppressing growth aggressivity. These properties reflect mechanisms great relevance to overcome overall management. This article highlights corresponding provides clinically illustrations framework 3P medicine primary (protection individuals at high risk against health-to-disease transition) secondary care progression). 3PM novelty makes good use patient phenotyping stratification, predictive multi-level diagnostics, application Artificial Intelligence (AI) tools individualized interpretation big data all proposed cost-effective tailored profiles clear benefits patients advanced

Язык: Английский

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Flavonoids Synergistically Enhance the Anti-Glioblastoma Effects of Chemotherapeutic Drugs

Biomolecules, Год журнала: 2021, Номер 11(12), С. 1841 - 1841

Опубликована: Дек. 7, 2021

Flavonoids are polyphenolic plant secondary metabolites with pleiotropic biological properties, including anti-cancer activities. These natural compounds have potential utility in glioblastoma (GBM), a malignant central nervous system tumor derived from astrocytes. Conventional GBM treatment modalities such as chemotherapy, radiation therapy, and surgical resection beneficial but limited by extensive invasion drug/radiation resistance. Therefore, dietary flavonoids-with demonstrated anti-GBM properties preclinical research-are alternative therapies. This review explores the synergistic enhancement of effects conventional chemotherapeutic drugs flavonoids. Primary studies published between 2011 2021 on flavonoid-chemotherapeutic synergy were obtained PubMed. demonstrate that flavonoids chrysin, epigallocatechin-3-gallate (EGCG), formononetin, hispidulin, icariin, quercetin, rutin, silibinin synergistically enhance canonical chemotherapeutics. mediated modulation intracellular signaling mechanisms related to apoptosis, proliferation, autophagy, motility, chemoresistance. In this light, hold promise improving current therapeutic strategies ultimately overcoming drug However, despite positive results, further investigations necessary before commencement clinical trials. Key considerations include bioavailability, blood-brain barrier (BBB) permeability, safety flavonoids; optimal dosages chemotherapeutics; delivery platforms; for adverse interactions.

Язык: Английский

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Application of Nano Drug Delivery System (NDDS) in Cancer Therapy: A Perspective

Recent Patents on Anti-Cancer Drug Discovery, Год журнала: 2022, Номер 18(2), С. 125 - 132

Опубликована: Июль 14, 2022

Background: Cancer is the biggest killer that threatens human health. Poor bioavailabil-ity and strong drug resistance of cancer drugs are common defects. In recent years, delivery therapy based on nanotechnology has become a focused research area, nano sys-tem been widely studied in treatment. Objective: Based articles patents published application systems treatment past five this paper summarizes types their advantages limitations order to provide reference for future anticancer systems. Methods: This perspective ad-vantages proposes development direction future. Results: review patents, we found system mainly divided into encapsulated covalently bound nano-prodrug system. Its reflected enhancing stability, improving bioavailability, reducing toxicity better diagnosis. However, new field science, some these might have high low bioavailability; off-target phenomenon often occurs, most stud-ies just early stage, its mechanism action, clinical efficacy patient toler-ance, remains be further investigated. Conclusion: systematically obtained last years. Future should consider potential risks, stable efficient designed treat can-cer by changing or functionalizing nanomaterial.

Язык: Английский

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Targeting Histone Deacetylases: Opportunities for Cancer Treatment and Chemoprevention

Pharmaceutics, Год журнала: 2022, Номер 14(1), С. 209 - 209

Опубликована: Янв. 16, 2022

The dysregulation of gene expression is a critical event involved in all steps tumorigenesis. Aberrant histone and non-histone acetylation modifications due to the abnormal activation deacetylases (HDAC) have been reported hematologic solid types cancer. In this sense, cancer-associated epigenetic alterations are promising targets for anticancer therapy chemoprevention. HDAC inhibitors (HDACi) induce hyperacetylation within target proteins, altering cell cycle proliferation, differentiation, regulation death programs. Over last three decades, an increasing number synthetic naturally derived compounds, such as dietary-derived products, demonstrated act HDACi provided biological molecular insights with regard role first part review focused on roles Zinc-dependent family malignant diseases. Accordingly, small-molecules natural products described terms cancer Furthermore, structural considerations included improve selectivity combinatory potential other specific targeting agents bifunctional proteolysis chimeras. Additionally, clinical trials that combine current therapies discussed, which may open new avenues feasibility HDACi’s future applications precision therapies.

Язык: Английский

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Alpinetin: A Review of Its Pharmacology and Pharmacokinetics

Frontiers in Pharmacology, Год журнала: 2022, Номер 13

Опубликована: Фев. 4, 2022

Flavonoids isolated from medicinal herbs have been utilized as valuable health-care agents due to their virous biological applications. Alpinetin is a natural flavonoid that emerges in many widely used plants, and has frequently applied Chinese patent drugs. Accumulated evidence demonstrated alpinetin possesses broad range of pharmacological activities such antitumor, antiinflammation, hepatoprotective, cardiovascular protective, lung antibacterial, antiviral, neuroprotective, other properties through regulating multiple signaling pathways with low systemic toxicity. However, pharmacokinetic studies documented may poor oral bioavailability correlated its extensive glucuronidation. Currently, the reported pharmacokinetics profiles are rare be scientifically reviewed. In this article, we aimed highlight mechanisms action various diseases strongly support curative potentials for prospective clinical We also summarized proposed some viable strategies convey an appreciable reference future advances drug development.

Язык: Английский

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Flavonoids Target Human Herpesviruses That Infect the Nervous System: Mechanisms of Action and Therapeutic Insights

Viruses, Год журнала: 2022, Номер 14(3), С. 592 - 592

Опубликована: Март 13, 2022

Human herpesviruses (HHVs) are large DNA viruses with highly infectious characteristics. HHVs can induce lytic and latent infections in their host, most of these neurotropic, the capacity to generate severe chronic neurological diseases peripheral nervous system (PNS) central (CNS). Treatment HHV based on strategies that include natural products-derived drugs is one rapidly developing fields modern medicine. Therefore, this paper, we lend insights into recent advances have been achieved during past five years utilizing flavonoids as promising for treatment such alpha-herpesviruses (herpes simplex virus type 1, 2, varicella-zoster virus), beta-herpesviruses (human cytomegalovirus), gamma-herpesviruses (Epstein–Barr Kaposi sarcoma-associated herpesvirus). The complications associated induced by reviewed emphasized. Additionally, work covers all possible mechanisms pathways which therapeutic actions against above-mentioned herpesviruses.

Язык: Английский

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Flavonoids-Based Delivery Systems towards Cancer Therapies

Bioengineering, Год журнала: 2022, Номер 9(5), С. 197 - 197

Опубликована: Май 2, 2022

Cancer is the second leading cause of death worldwide. Cervical cancer, for instance, considered a major scourge in low-income countries. Its development mostly associated with human papillomavirus persistent infection and despite availability preventive vaccines, they are only widely administered more developed countries, thus leaving large percentage unvaccinated women highly susceptible to this type cancer. Current treatments based on invasive techniques, being far from effective. Therefore, search novel, advanced personalized therapeutic approaches imperative. Flavonoids belong group natural polyphenolic compounds, well recognized their great anticancer capacity, promising be incorporated cancer therapy protocols. However, use limited due low solubility, stability bioavailability. To surpass these limitations, encapsulation flavonoids into delivery systems emerged as valuable strategy improve In context, aim review present most reliable flavonoids-based therapies progress accomplished, special focus cervical therapy. The gathered information revealed high potential highlights relevance application, allowing better understanding future studies effective

Язык: Английский

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