The effect of GLP-1R agonists on the medical triad of obesity, diabetes, and cancer

Cancer and Metastasis Reviews, Journal Year: 2024, Volume and Issue: 43(4), P. 1297 - 1314

Published: May 27, 2024

Glucagon-like peptide-1 receptor (GLP-1R) agonists have garnered significant attention for their therapeutic potential in addressing the interconnected health challenges of diabetes, obesity, and cancer. The role GLP-1R type 2 diabetes mellitus (T2DM) is highlighted, emphasizing its pivotal contribution to glucose homeostasis, promoting β-cell proliferation, facilitating insulin release. effectively managed obesity by reducing hunger, moderating food intake, regulating body weight. Beyond exhibit a multifaceted impact on cancer progression across various malignancies. mechanisms underlying these effects involve modulation signaling pathways associated with cell growth, survival, metabolism. However, current literature reveals lack vivo studies specific such as semaglutide, necessitating further research elucidate precise effects, particularly While other shown promising outcomes mitigating progression, association between some an increased risk remains topic requiring more profound investigation. This calls extensive unravel intricate relationships agonist different cancers, providing valuable insights clinicians researchers alike.

Language: Английский

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Resveratrol/Selenium Nanocomposite with Antioxidative and Antibacterial Properties

Nanomaterials, Journal Year: 2024, Volume and Issue: 14(4), P. 368 - 368

Published: Feb. 16, 2024

In this work, we synthesized a new composite material comprised of previously formulated resveratrol nanobelt-like particles (ResNPs) and selenium nanoparticles (SeNPs), namely ResSeNPs. Characterization was provided by FESEM optical microscopy, as well UV-Vis FTIR spectroscopy, the last showing hydrogen bonds between ResNPs SeNPs. DPPH, TBA, FRAP assays showed excellent antioxidative abilities with SeNPs contributing mainly to lipid peroxidation inhibition reducing/scavenging activity, respectively. The antibacterial effect against common medicinal implant colonizers pointed notably higher activity

Language: Английский

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Therapeutic potential of AMPK signaling targeting in lung cancer: Advances, challenges and future prospects

Life Sciences, Journal Year: 2021, Volume and Issue: 278, P. 119649 - 119649

Published: May 24, 2021

Language: Английский

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Flavonoids Synergistically Enhance the Anti-Glioblastoma Effects of Chemotherapeutic Drugs

Biomolecules, Journal Year: 2021, Volume and Issue: 11(12), P. 1841 - 1841

Published: Dec. 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.

Language: Английский

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Targeting lactate metabolism and glycolytic pathways in the tumor microenvironment by natural products: A promising strategy in combating cancer

BioFactors, Journal Year: 2021, Volume and Issue: 48(2), P. 359 - 383

Published: Nov. 1, 2021

Abstract Anticancer drugs are not purely effective because of their toxicity, side effects, high cost, inaccessibility, and associated resistance. On the other hand, cancer is a complex public health problem that could intelligently adopt different signaling pathways alter body's metabolism to escape from immune system. One strategies metastasize modifying pH in tumor microenvironment, ranging between 6.5 6.9. As powerful determiner, lactate responsible for this acidosis. It involved stimulation, including innate adaptive immunity, apoptotic‐related factors (Bax/Bcl‐2, caspase), glycolysis (e.g., GLUT‐1, PKM2, PFK, HK2, MCT‐1, LDH). Lactate metabolism, turn, interconnected with several dysregulated mediators, PI3K/Akt/mTOR, AMPK, NF‐κB, Nrf2, JAK/STAT, HIF‐1α. Because lactate's emerging critical role, targeting production its transporters important preventing managing tumorigenesis. Hence, exploring developing novel promising anticancer agents minimize human cancers urgent. Based on numerous studies, natural secondary metabolites as multi‐target alternative compounds health‐promoting properties possess more effectiveness low effects than conventional agents. Besides, mechanism multi‐targeted sources related cancer‐associated cross‐talked factors. This review focuses metabolism/transporters, lactate‐associated glycolytic pathways. mediators also targeted by products. Accordingly, plant‐derived introduced therapies combating through modulating

Language: Английский

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Natural Compounds in Glioblastoma Therapy: Preclinical Insights, Mechanistic Pathways, and Outlook

Cancers, Journal Year: 2021, Volume and Issue: 13(10), P. 2317 - 2317

Published: May 12, 2021

Glioblastoma (GBM) is an aggressive, often fatal astrocyte-derived tumor of the central nervous system. Conventional medical and surgical interventions have greatly improved survival rates; however, heterogeneity, invasiveness, chemotherapeutic resistance continue to pose clinical challenges. As such, dietary natural substances—an integral component lifestyle medicine approach chronic diseases—are examined as potential agents. These heterogenous substances exert anti-GBM effects by upregulating apoptosis autophagy, inducing cell cycle arrest, interfering with metabolism, inhibiting proliferation, neuroinflammation, chemoresistance, angiogenesis, metastasis. Although these beneficial are promising, substances’ efficacy in GBM constrained their bioavailability blood–brain barrier permeability; various chemical formulations proposed improve pharmacological properties. Many reviewed available over-the-counter supplements, underscoring viability interventions. However, trials remain necessary substantiate vitro vivo properties substances.

Language: Английский

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Resveratrol-like Compounds as SIRT1 Activators

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(23), P. 15105 - 15105

Published: Dec. 1, 2022

The sirtuin 1 (SIRT1) activator resveratrol has emerged as a promising candidate for the prevention of vascular oxidative stress, which is trigger endothelial dysfunction. However, its clinical use limited by low oral bioavailability. In this work, we have applied previously developed computational protocol to identify most derivatives from our in-house chemical library derivatives. compounds in terms SIRT1 activation and bioavailability, predicted silico, were evaluated their ability activate isolated enzyme. Then, assessed antioxidant effects effective derivative, compound 3d, human umbilical vein cells (HUVECs) injured with H2O2 100 µM. 3d significantly preserved cell viability prevented an intracellular reactive oxygen species increase HUVECs exposed stimulus. Such partially reduced presence inhibitor, sirtinol, confirming potential role sirtuins activity Although appeared less than activating enzyme, exhibited both almost superimposable, suggesting higher cross membranes target SIRT1.

Language: Английский

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Curcumin, calebin A and chemosensitization: How are they linked to colorectal cancer?

Life Sciences, Journal Year: 2023, Volume and Issue: 318, P. 121504 - 121504

Published: Feb. 20, 2023

Language: Английский

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Salvia officinalis L. exerts oncostatic effects in rodent and in vitro models of breast carcinoma

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: Feb. 23, 2024

Introduction: Based on extensive data from oncology research, the use of phytochemicals or plant-based nutraceuticals is considered an innovative tool for cancer management. This research aimed to analyze oncostatic properties Salvia officinalis L. [Lamiaceae; Salviae herba] using animal and in vitro models breast carcinoma (BC). Methods: The effects dietary administered S. two concentrations (0.1%/SAL 0.1/and 1%/SAL 1/) were assessed both syngeneic 4T1 mouse chemically induced rat BC. histopathological molecular evaluations rodent specimens performed after autopsy. Besides, numerous analyses human cell lines performed. Results Conclusion: dominant metabolites found propylene glycol extract (SPGE) representatives phenolics, specifically rosmarinic, protocatechuic, salicylic acids. Furthermore, occurrence triterpenoids ursolic oleanolic acid was proved SPGE. In a model, non-significant tumor volume decrease treatment associated with significant reduction mitotic activity index tumors by 37.5% (SAL 0.1) 31.5% 1) vs. controls (set as blank group not applied salvia diet). addition, at higher doses significantly decreased necrosis/whole area ratio 46% when compared control samples. chemoprevention study, dose lengthened latency 8.5 days improved high/low-grade carcinomas doses. Analyses mechanisms anticancer activities S . included well-validated prognostic, predictive, diagnostic biomarkers that are practice preclinical investigation. Our assessment vivo revealed changes comparison treated untreated cells. this regard, we overexpression caspase-3, increased Bax/Bcl-2 ratio, MDA, ALDH1, EpCam expression. reduced TGF-β serum levels rats (decrease IL-6 TNF-α borderline significance). Evaluation epigenetic modifications decline lysine methylations H3K4m3 increase acetylation H4K16ac groups. relative oncogenic miR21 tumor-suppressive miR145 (miR210, miR22, miR34a, miR155 altered). methylation ATM PTEN promoters ( PITX2, RASSF1 , TIMP3 Analyzing plasma metabolomics profile tumor-bearing rats, ketoacids derived BCAAs treatment. anti-cancer SPGE MCF‐7 MDA-MB-231 (cytotoxicity, caspase‐3/-7, Bcl‐2, Annexin V/PI, cycle, BrdU, mitochondrial membrane potential). study demonstrates chemopreventive haulm BC models.

Language: Английский

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Resveratrol as Chemosensitizer Agent: State of Art and Future Perspectives

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(4), P. 2049 - 2049

Published: Feb. 19, 2021

Resistance to chemotherapy still remains a major challenge in the clinic, impairing quality of life and survival rate patients. The identification unconventional chemosensitizing agents is therefore an interesting aspect cancer research. Resveratrol has emerged last decades as fascinating molecule, able modulate several cancer-related molecular mechanisms, suggesting possible application adjuvant management. This review goes deep into existing literature concerning effect resveratrol associated with most conventional chemotherapeutic drugs. Despite promising effects observed different types vitro studies, clinical translation presents strong limitations due low bioavailability resveratrol. Recently, efforts have been moved field drug delivery identifying strategies/formulations useful for more effective administration. necessity huge implementation this research area, appears molecule sensitize resistant tumors drugs, its potential use therapy-refractory

Language: Английский

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