Related Experiment Video
Updated: May 22, 2025
Author Spotlight: Exploring Photodynamic Therapy with Curcumin in a Murine Model for Oral Candidiasis
Published on: October 27, 2023
Panduratin A from Boesenbergia rotunda Effectively Inhibits EGFR/STAT3/Akt Signaling Pathways, Inducing Apoptosis in
Wanna Eiamart1,2, Piyanuch Wonganan3, Sarin Tadtong4
1Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Srinakharinwirot University, Nakhon Nayok 26120, Thailand.
Abstract:
Non-small cell lung cancer (NSCLC) is a challenging disease, with the epidermal growth factor receptor (EGFR) being a key target for new, effective treatments crucial for the signaling pathways regulating cancer cell survival. Targeting EGFR-mediated signaling offers promising strategies to improve NSCLC therapies, particularly in overcoming resistance in EGFR-mutant lung cancer. In this study, we investigated the anticancer effects of panduratin A, a naturally occurring flavonoid from Boesenbergia rotunda, on human NSCLC cell lines expressing both wild-type EGFR (A549) and mutant EGFR (H1975) using in vitro experiments and molecular docking approaches. Cytotoxicity screening revealed that panduratin A exhibits potent effects on both A549 (IC50 of 6.03 ± 0.21 µg/mL) and H1975 (IC50 of 5.58 ± 0.15 µg/mL) cell lines while demonstrating low toxicity to normal MRC5 lung cells (12.96 ± 0.36 µg/mL). Furthermore, western blotting and flow cytometric analyses indicated that panduratin A induces apoptosis by inhibiting p-EGFR and its downstream effectors, p-STAT3 and p-Akt, in lung cancer cells. Additionally, the docking study showed lower binding energy between panduratin A and the target proteins, comparable to that of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs). The ADMET prediction also highlighted panduratin A's exceptional drug-like properties. This study concludes that panduratin A shows significant promise as an anti-lung cancer candidate for NSCLC, offering an economical and effective strategy.
Insights
Panduratin A, a natural compound, effectively targets both wild-type and mutant epidermal growth factor receptor (EGFR) in non-small cell lung cancer (NSCLC) cells. It induces apoptosis and shows promise as an economical anti-lung cancer therapy.
Area of Science:
- Oncology
- Pharmacology
- Natural Products Chemistry
Background:
- Non-small cell lung cancer (NSCLC) necessitates novel therapeutic strategies, particularly targeting the epidermal growth factor receptor (EGFR) signaling pathway.
- Resistance to existing EGFR-targeted therapies remains a significant clinical challenge in NSCLC treatment.
Purpose of the Study:
- To evaluate the anticancer potential of panduratin A, a flavonoid from *Boesenbergia rotunda*, against human NSCLC cell lines with wild-type and mutant EGFR.
- To investigate the molecular mechanisms underlying panduratin A's anti-NSCLC effects, including apoptosis induction and signaling pathway inhibition.
Main Methods:
- In vitro cytotoxicity assays were performed on NSCLC cell lines (A549, H1975) and normal lung cells (MRC5).
- Western blotting and flow cytometry were used to analyze apoptosis and key signaling proteins (p-EGFR, p-STAT3, p-Akt).
- Molecular docking and ADMET predictions were employed to assess panduratin A's binding affinity and drug-like properties.
Main Results:
- Panduratin A demonstrated potent cytotoxicity against both A549 (IC50=6.03 µg/mL) and H1975 (IC50=5.58 µg/mL) cells, with low toxicity to normal MRC5 cells (IC50=12.96 µg/mL).
- Panduratin A induced apoptosis by inhibiting phosphorylated EGFR (p-EGFR) and its downstream targets, p-STAT3 and p-Akt.
- Molecular docking revealed favorable binding energy of panduratin A to EGFR, comparable to known EGFR tyrosine kinase inhibitors (TKIs), and favorable ADMET predictions.
Conclusions:
- Panduratin A exhibits significant anticancer activity against NSCLC cells, targeting key components of the EGFR pathway.
- Its potent efficacy, low toxicity, and favorable drug-like properties position panduratin A as a promising candidate for NSCLC therapy.
- Panduratin A represents a potential economical and effective therapeutic strategy for non-small cell lung cancer.
