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. 2023 Aug 8;8(33):30630-30639.
doi: 10.1021/acsomega.3c04314. eCollection 2023 Aug 22.

A New Saponin (Zygo-albuside D) from Zygophyllum album Roots Triggers Apoptosis in Non-Small Cell Lung Carcinoma (A549 Cells) through CDK-2 Inhibition

Enas E Eltamany  1 , Mohamed S Nafie  2 , Dina M Hal  1 , Maged S Abdel-Kader  3   4 , Abdelghafar M Abu-Elsaoud  5   6 , Safwat A Ahmed  1 , Amany K Ibrahim  1 , Jihan M Badr  1 , Reda F A Abdelhameed  1   7
Affiliations

A New Saponin (Zygo-albuside D) from Zygophyllum album Roots Triggers Apoptosis in Non-Small Cell Lung Carcinoma (A549 Cells) through CDK-2 Inhibition

Enas E Eltamany et al. ACS Omega. .

Abstract

Phytochemical study of the ethyl acetate root extract of Zygophyllum album has resulted in the isolation of a new saponin, Zygo-albuside D (1), along with two known compounds; (3-O-[β-D-quinovopyranosyl]-quinovic acid) (2), which is first reported in the root, and catechin (3), first reported in the genus. Their chemical structures were established by NMR and high-resolution mass spectrometry (HRMS). The new saponin (1) exhibited promising cytotoxicity with IC50 values of 3.5 and 5.52 μM on A549 and PC-3 cancer cell lines, respectively, compared to doxorubicin with IC50 values of 9.44 and 11.39 μM on A549 and PC-3 cancer cell lines, respectively. While it had an IC50 value of 46.8 μM against WISH cells. Investigating apoptosis-induction, compound 1 induced total apoptotic cell death in A549 lung cancer cells by 32-fold; 21.53% compared to 0.67% in the untreated control cells. Finally, it upregulated the pro-apoptotic genes and downregulated the antiapoptotic gene using gene expression levels. Compound 1 exhibited remarkable CDK-2 target inhibition by 96.2% with an IC50 value of 117.6 nM compared to Roscovitine. The molecular docking study further confirmed the binding affinity of compound 1 as CDK2 and Bcl2 inhibitors that led to apoptosis induction in A549 cancer cells. Hence, this study highlights the importance of compound 1 in the design of a new anticancer agent with specific mechanisms.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Chemical structures of isolated compounds.
Figure 2
Figure 2
Key COSY and HMBC correlations of compound 1.
Figure 3
Figure 3
Annexin V/PI labeling of untreated (control) and compound 1-treated A549 cells (IC50 = 2.34 μM, 48h) (A): Cytograms forapoptosis-necrosis assessment, “Q1: Necrosis, Q2: Late apoptosis, Q4: Early apoptosis’’. (B): Bar representation of apoptosis-necrosis assessment. Values are expressed as Mean ± SD of three independent trials, *(p ≤ 0.05) significant differences between treated and untreated cells employing unpaired t-test by GraphPad prism.
Figure 4
Figure 4
Gene expression analysis of A549 cells treated with compound 1 (IC50 = 2.34 μM, 48h) and untreated cells. The house-keeping gene was β-actin. 2−ΔΔCT was employed to calculate the fold of change, where ΔΔCT is the difference between mean values of genes CT values in the treated and control groups. Values are expressed as the mean ± SD of three independent trials. Bars followed by different letters are significantly different according to DMRTs at the 0.05 level.
Figure 5
Figure 5
Ligand–receptor binding dispositions of docked compound 1 inside the CDK-2 and Bcl-2 proteins. A: Surface-view and B: Interactive view with the key amino acids Lys 89 (CDK-2) and Arg 66 (Bcl-2).
See this image and copyright information in PMC

References

    1. Costea T.; Vlad O. C.; Miclea L. C.; Ganea C.; Szöllősi J.; Mocanu M. M. Alleviation of multidrug resistance by flavonoid and non-flavonoid compounds in breast, lung, colorectal and prostate cancer. Int. J. Mol. Sci. 2020, 21, 401.10.3390/ijms21020401. - DOI - PMC - PubMed
    1. Eguchi H.; Kimura R.; Matsunaga H.; Matsunaga T.; Yoshino Y.; Endo S.; Ikari A. Increase in Anticancer Drug-Induced Toxicity by Fisetin in Lung Adenocarcinoma A549 Spheroid Cells Mediated by the Reduction of Claudin-2 Expression. Int. J. Mol. Sci. 2022, 23, 7536.10.3390/ijms23147536. - DOI - PMC - PubMed
    1. Jain S.; Dwivedi J.; Jain P. K.; Satpathy S.; Patra A. Medicinal plants for treatment of cancer: A brief review. Pharmacogn J. 2016, 8, 87.10.5530/pj.2016.2.1. - DOI
    1. Sethi G.; Shanmugam M. K.; Warrier S.; Merarchi M.; Arfuso F.; Kumar A. P.; Bishayee A. Pro-Apoptotic and Anti-Cancer Properties of Diosgenin: A Comprehensive and Critical Review. Nutrients 2018, 10, 645.10.3390/nu10050645. - DOI - PMC - PubMed
    1. Abdelhameed R. F.; Habib E. S.; Ibrahim A. K.; Yamada K.; Abdel-Kader M. S.; Ahmed S. A.; Ibrahim A. K.; Badr J. M.; Nafie M. S. Chemical constituent profiling of Phyllostachys heterocycla var. Pubescens with selective cytotoxic polar fraction through EGFR inhibition in HepG2 cells. Molecules 2021, 26, 940.10.3390/molecules26040940. - DOI - PMC - PubMed