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Published on: August 23, 2024
Dieckol inhibits non-small-cell lung cancer cell proliferation and migration by regulating the PI3K/AKT signaling
Chun-Hong Wang1, Xiao-Feng Li1, Li-Fang Jin1
1Department of Oncology and Hematology, The Second Hospital of Jilin University, Changchun, Jilin, China.
Abstract:
Non-small-cell lung cancer (NSCLC) is one of the most prevalent type of lung cancers with an increased mortality rate in both developed and developing countries worldwide. Dieckol is one such polyphenolic drug extracted from brown algae which has proven antioxidant and anti-inflammatory properties. In the present study, we evaluated the anticancer property of dieckol against NSCLC cell line A549. The LC50 value of dieckol was found to be 25 µg/mL by performing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the antiapoptotic property of dieckol was analyzed by dual staining technique with acridine orange/propidium iodide (AO/PI) stains. It was further confirmed with flow cytometry analysis with Annexin FITC and JC-1 staining and the anti-invasive property was assessed by Transwell assay. The molecular mechanism of dieckol anticancer activity was confirmed by estimating the levels of caspases and by estimating the signaling proteins of Pi3K/AKT/mTOR signaling pathway using the immunoblotting technique. Our data suggest that dieckol is potent anticancer agent, it effectively inhibits the invasive and migratory property A549 cells and it also induces apoptosis via inhibiting Pi3K/AKT/mTOR signaling, activating the tumor suppressor protein E-cadherin signifying that dieckol is potent natural anticancer drug to treat NSCLC.
Insights
Dieckol, a compound from brown algae, effectively inhibits non-small-cell lung cancer (NSCLC) cell invasion and migration. It induces apoptosis by impacting the PI3K/AKT/mTOR pathway, suggesting its potential as a natural anticancer drug for NSCLC.
Area of Science:
- Pharmacology
- Oncology
- Natural Products Chemistry
Background:
- Non-small-cell lung cancer (NSCLC) presents a significant global health challenge with high mortality rates.
- Dieckol, a polyphenol from brown algae, exhibits known antioxidant and anti-inflammatory effects.
Purpose of the Study:
- To investigate the anticancer properties of dieckol against the A549 NSCLC cell line.
- To elucidate the molecular mechanisms underlying dieckol's anti-cancer activity.
Main Methods:
- Cytotoxicity assessed via MTT assay (LC50 = 25 µg/mL).
- Apoptosis evaluated using acridine orange/propidium iodide (AO/PI) and Annexin FITC/JC-1 staining via flow cytometry.
- Invasiveness assessed using Transwell assays.
- Molecular mechanisms explored through caspase level determination and immunoblotting of the PI3K/AKT/mTOR pathway.
Main Results:
- Dieckol demonstrated significant inhibition of A549 cell invasion and migration.
- Dieckol induced apoptosis in NSCLC cells.
- The compound suppressed the PI3K/AKT/mTOR signaling pathway and activated the tumor suppressor E-cadherin.
Conclusions:
- Dieckol exhibits potent anticancer activity against NSCLC cells.
- Dieckol functions as an anti-invasive and pro-apoptotic agent by modulating key cellular pathways.
- Dieckol represents a promising natural compound for the development of novel NSCLC therapeutics.
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