Carpobrotus edulis Flower Extract Exerts Cytotoxic and Apoptotic Effects on A-549 Lung Cancer Cells: Phytochemical Profiling and In Silico EGFR Interaction Screening
10 affiliations
- 1Department of Pharmaceutical Chemistry, College of Pharmacy, University of Hail, Hail 81442, Saudi Arabia
- 2Medical and Diagnostic Research Centre, University of Hail, Hail 55473, Saudi Arabia
- 3Department of Biochemistry, Egyptian Drug Authority (Formerly National Organization for Drug Control and Research), Giza 12553, Egypt
- 4Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Egyptian Russian University, Cairo 11829, Egypt
- 5Drug Design and Discovery Laboratory, Helmy Institute for Medical Sciences, Zewail City of Science and Technology, 6th of October City 12578, Egypt
- 6Department of Clinical Pharmacy, College of Pharmacy, University of Hail, Hail 81442, Saudi Arabia
- 7Department of Pharmaceutics and Industrial Pharmacy, College of Pharmacy, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia
- 8College of Pharmacy, University of Hail, Hail 81442, Saudi Arabia
- 9Department of Pharmacognosy, Faculty of Pharmacy, University of Sadat City, Sadat City 32897, Egypt
- 10Faculty of Pharmacy, National University of Sadat City, Sadat City 32897, Egypt
Abstract
Medicinal plants serve as critical reservoirs of bioactive scaffolds for targeted cancer therapeutics. This study evaluated the antiproliferative potential of Carpobrotus edulis methanolic flower extract across a panel of human cancer cell lines, including pancreatic (Panc-1), breast (MCF-7), liver (HepG-2), and lung (A-549) malignancies. Screening assays revealed potent, dose-dependent cytotoxicity in an MTT-based viability assay, with A-549 lung cancer cells being the most sensitive of the four tested cancer cell lines (IC50 = 3.62 ± 0.34 μg/mL). Selectivity over non-malignant cells was not assessed. Flow cytometry showed an increase in the S-phase fraction and in Annexin V-positive cells, and ELISA showed higher Bax and p53 and lower Bcl-2 in extract-treated A-549 cells, consistent with apoptosis through the intrinsic pathway. The measured caspase-3 concentration was lower after treatment, and the assay does not distinguish pro-caspase-3 from cleaved caspase-3. Phytochemical profiling via GC-MS identified a diverse array of bioactive metabolites, predominantly triterpenoids, phytosterols, fatty acid derivatives, and cyclitols. To explore EGFR as a putative target, an in vitro EGFR kinase assay was combined with molecular docking and molecular dynamics (MD) simulations. Among the profiled metabolites, the cyclitol derivative mome inositol displayed the most favorable docking score binding affinity toward the EGFR kinase domain (−7.35 kcal/mol), establishing robust hydrogen-bonding networks with key catalytic residues within the active site. Furthermore, a 100 ns MD simulation revealed the relative thermodynamic stability of the mome inositol–EGFR complex with more favorable RMSD, RMSF, hydrogen bond and radius of gyration profiles than the co-crystallized reference ligand. Collectively, these integrated in vitro, phytochemical, and in silico findings indicate that methanolic extract of C. edulis flowers exerts potent anticancer activity predominantly through mitochondrial-mediated apoptosis complemented by a computationally predicted interaction between its major cyclitol constituent and the EGFR kinase domain. These results establish the extract as a promising early-stage anticancer lead and provide a clear rationale for advancing to mechanistic studies, with in vivo validation reserved for subsequent investigations.
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BibTeX
@article{huwaimel2026carpobrotus,
title = {{Carpobrotus edulis Flower Extract Exerts Cytotoxic and Apoptotic Effects on A-549 Lung Cancer Cells: Phytochemical Profiling and In Silico EGFR Interaction Screening}},
author = {Bader Huwaimel and Amr S. Abouzied and Marwa M. Abd Rabo and Mohamed A. Said and Saad Alqarni and Ali Alghubayshi and Hashem O. Alsaab and Rami M. Alzhrani and Wejdan S. Alshehri and Nouf Eid Alrashidi and Lamya A. Alwahdani and Kareem M. Younes and Mohamed S. Refaey},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = nov,
doi = {10.3390/ijms272110016},
url = {https://www.mdpi.com/1422-0067/27/21/10016},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Carpobrotus edulis Flower Extract Exerts Cytotoxic and Apoptotic Effects on A-549 Lung Cancer Cells: Phytochemical Profiling and In Silico EGFR Interaction Screening
AU - Bader Huwaimel
AU - Amr S. Abouzied
AU - Marwa M. Abd Rabo
AU - Mohamed A. Said
AU - Saad Alqarni
AU - Ali Alghubayshi
AU - Hashem O. Alsaab
AU - Rami M. Alzhrani
AU - Wejdan S. Alshehri
AU - Nouf Eid Alrashidi
AU - Lamya A. Alwahdani
AU - Kareem M. Younes
AU - Mohamed S. Refaey
PY - 2026
DA - 2026/11/08
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms272110016
UR - https://www.mdpi.com/1422-0067/27/21/10016
AB - Medicinal plants serve as critical reservoirs of bioactive scaffolds for targeted cancer therapeutics. This study evaluated the antiproliferative potential of Carpobrotus edulis methanolic flower extract across a panel of human cancer cell lines, including pancreatic (Panc-1), breast (MCF-7), liver (HepG-2), and lung (A-549) malignancies. Screening assays revealed potent, dose-dependent cytotoxicity in an MTT-based viability assay, with A-549 lung cancer cells being the most sensitive of the four tested cancer cell lines (IC50 = 3.62 ± 0.34 μg/mL). Selectivity over non-malignant cells was not assessed. Flow cytometry showed an increase in the S-phase fraction and in Annexin V-positive cells, and ELISA showed higher Bax and p53 and lower Bcl-2 in extract-treated A-549 cells, consistent with apoptosis through the intrinsic pathway. The measured caspase-3 concentration was lower after treatment, and the assay does not distinguish pro-caspase-3 from cleaved caspase-3. Phytochemical profiling via GC-MS identified a diverse array of bioactive metabolites, predominantly triterpenoids, phytosterols, fatty acid derivatives, and cyclitols. To explore EGFR as a putative target, an in vitro EGFR kinase assay was combined with molecular docking and molecular dynamics (MD) simulations. Among the profiled metabolites, the cyclitol derivative mome inositol displayed the most favorable docking score binding affinity toward the EGFR kinase domain (−7.35 kcal/mol), establishing robust hydrogen-bonding networks with key catalytic residues within the active site. Furthermore, a 100 ns MD simulation revealed the relative thermodynamic stability of the mome inositol–EGFR complex with more favorable RMSD, RMSF, hydrogen bond and radius of gyration profiles than the co-crystallized reference ligand. Collectively, these integrated in vitro, phytochemical, and in silico findings indicate that methanolic extract of C. edulis flowers exerts potent anticancer activity predominantly through mitochondrial-mediated apoptosis complemented by a computationally predicted interaction between its major cyclitol constituent and the EGFR kinase domain. These results establish the extract as a promising early-stage anticancer lead and provide a clear rationale for advancing to mechanistic studies, with in vivo validation reserved for subsequent investigations.
SN - 1422-0067
ER -