Related Experiment Video
Updated: May 22, 2025
Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway
Published on: August 23, 2024
Involvement of GSK-3β, NF-κB, PPARγ, and apoptosis in amlodipine's anticancer effect in BALB/c mice
El-Shaimaa A Arafa1, Maha M Abdel-Fattah2, Emad H M Hassanein3
1College of Pharmacy and Health Sciences, Ajman University, Ajman 346, United Arab Emirates; Center of Medical and Bio-Allied Health Sciences Research, Ajman University, Ajman 346, United Arab Emirates; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt.
Abstract:
Lung cancer is the primary cause of death due to cancer all over the world despite the decrease in the mortality rates from cancer in general. While chemotherapy is a commonly employed treatment for lung cancer, its efficacy is limited due to poor tissue selectivity, inadequate delivery to tumor sites, and associated side effects. The present work aims to assess the potential anti-cancer effectiveness of amlodipine, a calcium channel blocker, on murine lung cancer via modulating GSK-3β, NF-κB, PPARγ, and apoptosis. Lung cancer was induced in BALB/c mice by intraperitoneal injection of 1.5 g/kg in two doses of urethane: once on the 1st and the second on the 60th day of the experiment. Amlodipine was administered orally at a dose of 10 mg/kg/day for the last 28 days of experiment. Relative to urethane group, amlodipine mitigated urethane-induced histopathological abnormalities. It restored oxidant/antioxidant balance by normalizing MDA, GSH, and SOD. Furthermore, it exerted a marked anti-inflammatory effect through downregulating lung MPO, ICAM-1, IL-6, TNF-α, and NF-қB expressions. Amlodipine enhanced apoptosis of cancer cells as evidenced by increasing Bax and decreasing Bcl-2 expression. The anticancer effect of amlodipine was suggested to be mediated through increasing PPARγ and reducing GSK3β and p-GSK3β signaling. Collectively, these results suggest that amlodipine could exert a promising anticancer effect against lung cancer through modulating GSK-3β, NF-κB, PPARγ, and apoptosis. Our findings could be highly significant in clinical settings, offering a valuable adjuvant option for managing lung carcinoma, particularly in patients with cardiovascular disorders.
Insights
Amlodipine, a calcium channel blocker, demonstrated significant anti-cancer effects in a murine lung cancer model. It reduced tumor progression by modulating key molecular pathways and enhancing cancer cell apoptosis, suggesting its potential as an adjuvant therapy.
Area of Science:
- Pharmacology and Toxicology
- Cancer Biology and Therapeutics
- Molecular Medicine
Background:
- Lung cancer remains a leading cause of cancer-related mortality worldwide.
- Current chemotherapy for lung cancer faces limitations including poor selectivity, inadequate tumor delivery, and significant side effects.
- There is a need for novel therapeutic strategies, potentially including repurposed drugs, to improve lung cancer treatment outcomes.
Purpose of the Study:
- To investigate the anti-cancer potential of amlodipine, a calcium channel blocker, in a chemically induced murine lung cancer model.
- To elucidate the molecular mechanisms underlying amlodipine's effects, focusing on modulation of GSK-3β, NF-κB, PPARγ, and apoptosis.
- To assess amlodipine's impact on oxidative stress, inflammation, and histopathological changes in lung tissue.
Main Methods:
- Lung cancer was induced in BALB/c mice using urethane.
- Amlodipine was administered orally at 10 mg/kg/day for the final 28 days of the experiment.
- Evaluated histopathological changes, oxidant/antioxidant balance (MDA, GSH, SOD), inflammatory markers (MPO, ICAM-1, IL-6, TNF-α, NF-κB), apoptosis markers (Bax, Bcl-2), and signaling pathways (GSK-3β, PPARγ).
Main Results:
- Amlodipine significantly mitigated urethane-induced lung histopathological abnormalities.
- It restored oxidant/antioxidant balance and exerted marked anti-inflammatory effects by downregulating key inflammatory markers and NF-κB.
- Amlodipine enhanced cancer cell apoptosis (increased Bax/decreased Bcl-2) and its effects were linked to increased PPARγ and reduced GSK-3β signaling.
Conclusions:
- Amlodipine exhibits promising anti-cancer activity against lung cancer in a murine model.
- The anti-cancer effects are mediated through modulation of GSK-3β, NF-κB, PPARγ pathways, and induction of apoptosis.
- Amlodipine represents a potential valuable adjuvant therapeutic option for lung carcinoma, especially in patients with co-existing cardiovascular conditions.
More Related Videos
08:15Author Spotlight: Network Pharmacology and Molecular Docking to Decipher the Action of Jiawei Shengjiang San Against Diabetic Kidney Disease
Published on: May 10, 2024
10:09Drug Treatment by Central Venous Catheter in a Mouse Model of Angiotensin II Induced Abdominal Aortic Aneurysm and Monitoring by 3D Ultrasound
Published on: August 4, 2022
