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Current Bioactive Compounds

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ISSN (Print): 1573-4072
ISSN (Online): 1875-6646

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Research Article

Selective Cytotoxic Constituents from Gardenia latifolia and their In Silico Topoisomerase IIα Inhibition

Author(s): Asmaa M. Selim, Soad A. L. Bayoumi, Anber F. Mohammed, Enaam Y. Backheet and Shaymaa M. Mohamed*

Volume 18, Issue 8, 2022

Published on: 19 April, 2022

Article ID: e040322201687 Pages: 9

DOI: 10.2174/1573407218666220304094123

Price: $65

Abstract

Background: The search for natural anticancer agents is a worthy scientific research goal, driven by the hope to lessen cancer's tremendous global burden.

Objective: This study aimed at evaluating the cytotoxic activity of Gardenia latifolia Ait. (Rubiaceae) against lung (A549) and colon (HCT116) cancer cell lines. Cytotoxicity-guided isolation of the bioactive phytochemicals was conducted, followed by various mechanistic validations of the appealing cytotoxic metabolites.

Methods: The cytotoxic effects were determined using an MTT assay. The two most cytotoxic compounds were further evaluated for their effects on cell cycle progression and apoptotic capabilities using the flow cytometry approach. Additionally, we conducted a molecular docking analysis to reveal their potential interactions with the human topoisomerase IIα.

Results: The phytochemical investigation afforded nine compounds, including a new one, (-) 1- acetyl 4,5-di-O-caffeoylquinic acid. The latter compound was the most cytotoxic against the colon cancer cell line (IC50 1.9 μg/ml) with a remarkable tumor-selectivity (SI ≈ 15). Moreover, the isolated glycoside, 1-O- [6-O- (5-O-vanilloyl- β-ᴅ-apiofuranosy1)- β-ᴅ-glucopyranosy1]-3,4,5- trimethoxybenzene, showed selective cytotoxicity towards A549 and HCT116 cells (IC50 values of 3.8 and 3.3 μg/ml, respectively). Both compounds considerably affected the cell cycle distribution. They caused G2/M cell cycle arrest, showed apoptotic capabilities, and displayed significant in silico topoisomerase IIα inhibition.

Conclusion: Two cytotoxic and apoptotic compounds were reported from Gardenia latifolia. Subsequent in vivo studies and clinical trials should be conducted to substantiate their anticipated therapeutic values.

Keywords: Gardenia latifolia Rubiaceae cytotoxicity apoptosis molecular docking topoisomerase IIα inhibition.

Graphical Abstract

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