Chemo Preventive Potential of Rutin-Rich Extract Obtained from Capparis spinosa Culture against HepG2 Cancer Cell Line Activity

Document Type : Original Article

Authors

1 Medicinal and Aromatic Plants, Tissue Culture and Germplasm Conservation Lab. Hort. Res. Inst. Agric. Res. Centre, Egypt

2 Biochemistry Department, Faculty of Agriculture, Cairo University, Giza, Egypt.

3 Biochemistry Department, Faculty of Agriculture, Cairo University, P. Box 12613, Gamma St, Giza, Egypt

4 Medicinal and Aromatic Dept. Horti. Res. Institute, A. R. C., Egypt

Abstract

Capparis spinosa, an edible medicinal plant rich in flavonoids, relies on amino acids as key precursors for secondary metabolite biosynthesis in vitro. This study investigated the effects of tryptophan, glutamine, and phenylalanine at varying concentrations on callus growth, flavonoid production, and cytotoxic activity against the hepatocellular carcinoma cell line (HepG2). Callus induction was optimized using 3 mg/L 2,4-Dichlorophenoxyacetic acid (2,4-D), achieving a 44% callusing frequency from leaf explants. Elicitation with 100 mg/L tryptophan or 300 mg/L glutamine significantly enhanced callus biomass (4.7 g fresh weight). HPLC analysis revealed elevated rutin levels in callus treated with 100 mg/L glutamine (88.2 µg/g) or 200 mg/L phenylalanine (64.3 µg/g), highlighting their role in flavonoid biosynthesis. The glutamine-elicited extract (100 mg/L) exhibited potent cytotoxicity against HepG2 cells (IC50: 356.65 µg/mL), followed by phenylalanine treatment (IC50: 371.05 µg/mL). Molecular docking studies demonstrated rutin’s ability to suppress HepG2 proliferation by targeting promoter regions, downregulating oncogenic signaling pathways, and inhibiting spheroid formation. Mechanistically, rutin induced apoptosis and mitigated oxidative stress, underscoring its antitumor potential. These findings position amino acid elicitation as a viable strategy to enhance rutin yield in C. spinosa cultures, offering a sustainable platform for producing anticancer compounds. Further in silico and in vitro studies are warranted to explore rutin’s interactions with specific molecular targets in hepatocellular carcinoma.

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Articles in Press, Accepted Manuscript
Available Online from 25 June 2025
  • Receive Date: 09 April 2025
  • Revise Date: 17 May 2025
  • Accept Date: 22 June 2025