Anti-Diabetic Therapies and Cancer: From Bench to Bedside DOI Creative Commons
Dimitris Kounatidis, Natalia G. Vallianou, Ιrene Karampela

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 14(11), P. 1479 - 1479

Published: Nov. 20, 2024

Diabetes mellitus (DM) is a significant risk factor for various cancers, with the impact of anti-diabetic therapies on cancer progression differing across malignancies. Among these therapies, metformin has gained attention its potential anti-cancer effects, primarily through modulation AMP-activated protein kinase/mammalian target rapamycin (AMPK/mTOR) pathway and induction autophagy. Beyond metformin, other conventional treatments, such as insulin, sulfonylureas (SUs), pioglitazone, dipeptidyl peptidase-4 (DPP-4) inhibitors, have also been examined their roles in biology, though findings are often inconclusive. More recently, novel medications, like glucagon-like peptide-1 (GLP-1) receptor agonists, dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) sodium-glucose co-transporter-2 (SGLT-2) revolutionized DM management by not only improving glycemic control but delivering substantial cardiovascular renal benefits. Given diverse metabolic including anti-obesogenic properties, agents now under meticulous investigation influence tumorigenesis advancement. This review aims to offer comprehensive exploration evolving landscape glucose-lowering treatments implications biology. It critically evaluates experimental evidence surrounding molecular mechanisms which medications may modulate oncogenic signaling pathways reshape tumor microenvironment (TME). Furthermore, it assesses translational research clinical trials gauge practical relevance real-world settings. Finally, explores adjuncts treatment, particularly enhancing efficacy chemotherapy, minimizing toxicity, addressing resistance within framework immunotherapy.

Language: Английский

Persisting blood–brain barrier disruption following cisplatin treatment in a mouse model of chemotherapy-associated cognitive impairment DOI Creative Commons
Roland Patai,

Boglarka Csik,

Ádám Nyúl‐Tóth

et al.

GeroScience, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 21, 2025

Abstract Chemotherapy-related cognitive impairment, commonly referred to as “chemobrain,” significantly affects cancer survivors’ quality of life, yet its underlying mechanisms remain unclear. Most chemotherapeutic agents cannot cross the blood–brain barrier (BBB), they cause central nervous system side effects, suggesting alternative pathways toxicity. Given that these drugs interact with cerebrovascular endothelium at their highest concentrations, it is logical hypothesize endothelial damage contributes effects. Our recent studies demonstrated paclitaxel-induced impairment in a mouse model results partial BBB disruption and subsequent neuroinflammation, mediated by chemotherapy-induced senescence. In this pilot study, we used two-photon microscopy assess permeability mice receiving clinically relevant cisplatin regimen, evaluating leakage fluorescent dextran tracers varying molecular weights. Two months post-treatment, cisplatin-treated exhibited increased smaller (40 kDa, 3 0.3 kDa) compared controls, indicating sustained disruption. These align our findings for paclitaxel suggest senescence play role impairments. Interventions targeting health could mitigate long-term improving outcomes survivors.

Language: Английский

Citations

2
The reno-protective effect of Empagliflozin against carbon tetrachloride (CCl4)-induced nephrotoxicity in mice halting JNK/MKK4/NRF2/NF-KB pathway DOI

Amany A. Alzokaky,

Shimaa K Saber,

Mennatallah O. Zaki

et al.

Food and Chemical Toxicology, Journal Year: 2025, Volume and Issue: unknown, P. 115439 - 115439

Published: April 1, 2025

Language: Английский

Citations

0
Nephroprotective Potential of Lyophilized Grewia asiatica Powder Against Renal Biomarkers and Inflammation In Vivo DOI Creative Commons
Sherif Latif, Muhammad Sohaib, Sanaullah Iqbal

et al.

Journal of Nutrition and Metabolism, Journal Year: 2025, Volume and Issue: 2025(1)

Published: Jan. 1, 2025

Introduction: Phalsa ( Grewia asiatica ) fruit is known for its rich nutritional profile and diverse pharmacological properties such as antioxidants, anti‐inflammatory, anti‐cancer, making it a promising contender preventive measures against cisplatin‐induced acute kidney injury (AKI) in living organisms. Material Methods: In the present study, rats were provided with different levels of lyophilized asiatica, i.e., 200, 300, 400 mg/kg body weight along control, fed on basal diet. After trial completion, blood serum samples subjected to renal biomarkers, hematology, liver function tests, interleukin‐6 (IL‐6), whereas enzymes (alanine aminotransferase (ALT); sodium oxide dismutase, glutathione) tissues photomicrographs tissue damage measured. Results: The findings revealed that provision effectively reduced urea nitrogen, creatinine AKI well treatments demonstrated significant improvements antioxidant activity by reducing malonaldehyde increasing glutathione, catalase, superoxide dismutase groups treated dosages 300 powder. Conclusion: exhibited remarkable hepatoprotective decreasing ALT displayed anti‐inflammatory properties, evidenced substantial decrease levels. study also added valuable insight into multiform nephroprotective reverberation phalsa powder, emphasizing plausible protective use cisplatin‐induced​ nephrotoxicity.

Language: Английский

Citations

0
Empagliflozin enhances cisplatin activity in chemo-resistant EJ138 bladder cancer cells: The importance of anti-diabetic medications in cancer treatment DOI
Saeedeh Shariati, Shokooh Mohtadi, Shahrzad Molavinia

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: July 22, 2024

Abstract Background Anti-diabetic medications has been found to reduce chemotherapy resistance. This study sought investigate the role of Empagliflozin (Empa) as an anti-diabetic medication in reversing Cisplatin (Cis) resistance EJ138 bladder cancer (BC) cells. Materials and Methods The cell line was cultured divided into four groups: control, Cis-treated, Empa-treated, Cis + Empa-treated groups. effects and/or Empa on viability were determined using MTT technique. level ROS produced by cells evaluated green fluorescent dye dichloro-dihydro fluorescein (DCF). expression proteins involved glucose transport, proliferation, apoptosis, cycle invasion Western blotting. Data analyzed GraphPad prism software a One-way ANOVA test. All experiments repeated three times. presented Mean ± SEM. significant difference between groups calculated based P < 0.05. Results IC50 equal 16 mM for 72 µg/ml Empa. Treatment with caused increase SGLT2 (p 0.001). Conversely, group treated showed decrease compared control (P generation significantly elevated after treatment Cis, Empa, their combination downregulated AKT, PI3K, mTOR, Bax, MMP-2, MMP-9 However, Bcl2, P21, P53 following Protein differed across Cis-treated all other Conclusion exhibits beneficial anti-cancer activity against boosts BC through inhibition.

Language: Английский

Citations

0
The toxicity of cisplatin derives from effects on renal organic ion transporters expression and serum endogenous substance levels DOI
Mingkang Zhang,

Yile Li,

Yanrong Ma

et al.

Food and Chemical Toxicology, Journal Year: 2024, Volume and Issue: 192, P. 114949 - 114949

Published: Aug. 24, 2024

Language: Английский

Citations

0
Anti-Diabetic Therapies and Cancer: From Bench to Bedside DOI Creative Commons
Dimitris Kounatidis, Natalia G. Vallianou, Ιrene Karampela

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 14(11), P. 1479 - 1479

Published: Nov. 20, 2024

Diabetes mellitus (DM) is a significant risk factor for various cancers, with the impact of anti-diabetic therapies on cancer progression differing across malignancies. Among these therapies, metformin has gained attention its potential anti-cancer effects, primarily through modulation AMP-activated protein kinase/mammalian target rapamycin (AMPK/mTOR) pathway and induction autophagy. Beyond metformin, other conventional treatments, such as insulin, sulfonylureas (SUs), pioglitazone, dipeptidyl peptidase-4 (DPP-4) inhibitors, have also been examined their roles in biology, though findings are often inconclusive. More recently, novel medications, like glucagon-like peptide-1 (GLP-1) receptor agonists, dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) sodium-glucose co-transporter-2 (SGLT-2) revolutionized DM management by not only improving glycemic control but delivering substantial cardiovascular renal benefits. Given diverse metabolic including anti-obesogenic properties, agents now under meticulous investigation influence tumorigenesis advancement. This review aims to offer comprehensive exploration evolving landscape glucose-lowering treatments implications biology. It critically evaluates experimental evidence surrounding molecular mechanisms which medications may modulate oncogenic signaling pathways reshape tumor microenvironment (TME). Furthermore, it assesses translational research clinical trials gauge practical relevance real-world settings. Finally, explores adjuncts treatment, particularly enhancing efficacy chemotherapy, minimizing toxicity, addressing resistance within framework immunotherapy.

Language: Английский

Citations

0