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All Journal Narra J
Azizah, Norma N.
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Biochemistry, Genetics & Molecular Biology Health Professions Immunology & microbiology Medicine & Pharmacology Public Health

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Ethanol extract from Ziziphus nummularia stem inhibits MCF-7 breast cancer cell proliferation through TP53 regulating kinase (TP53RK)-mediated p53 activation: In silico and genes expression investigations Elya, Berna; Rosmalena, Rosmalena; Fajrin, Ajeng M.; Tedjo, Aryo; Ramadanti, Nur A.; Azizah, Norma N.; Hashim, Najihah BM.
Narra J Vol. 5 No. 1 (2025): April 2025
Publisher : Narra Sains Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.52225/narra.v5i1.1382

Abstract

The p53 signaling pathway plays a critical role in regulating the cell cycle, apoptosis, and senescence, making it a key target in cancer research. The aim of this study was to investigate the effects of an ethanol extract from the stem of Ziziphus nummularia on the proliferation and expression of genes involved in the p53 pathway in MCF-7 breast cancer cells. To achieve this, real-time quantitative PCR (RT-qPCR) was used to evaluate the mRNA expression of downstream genes linked to cell cycle and senescence, including CycE or CCNE1, RBL1, and E2F1. Molecular docking simulations using Molegro Virtual Docker (MVD) were also performed to assess the potential inhibitory activity of metabolite compounds from Z. nummularia stem against p53-regulating kinase (TP53RK). The results showed that the IC50 value of Z. nummularia stem ethanol extract against MCF-7 cells was 38.27±0.72 µg/mL. The results also revealed a reduction in the expression of downstream genes linked to cell senescence and the cell cycle: CycE or CCNE1 (p=0.011), RBL1 (p=0.008), and E2F1 (p=0.005), which was observed through RT-qPCR analysis of mRNA expression. This fact indicated that the inhibitory effects on proliferation by the ethanol extract of Z. nummularia stem might occur via pathways associated with cell senescence and cell cycle arrest.  Molecular docking results of metabolite compounds from Z. nummularia stem suggested that squalene (Rerank score -112.70 kJ/mol), and nummularine B (Rerank score -110.68 kJ/mol) had potential as TP53RK inhibitors. These Rerank scores were smaller compared to the Rerank score of adenyl-imidodiphosphate (AMP-PNP), which was the native ligand of TP53RK, as confirmed by molecular dynamics analysis. These in silico results were confirmed by the decrease in p21 (CDKN1A) mRNA expression. In conclusion, the anti-proliferative effects of the ethanol extract from Z. nummularia stem on breast cancer cells occurred by affecting cell cycle-related genes and inhibiting apoptosis protection mediated by overexpression of p21 (CDKN1A) through p53 activity.
Beetroot (Beta vulgaris) potential in preventing colorectal cancer using in-silico analysis Dwijayanti, Adisti; Azizah, Norma N.; Erlina, Linda; Kusmardi, Kusmardi; Ningsih, Sri S.; Fadilah, Fadilah; Hashim, Najihah M.
Narra J Vol. 5 No. 2 (2025): August 2025
Publisher : Narra Sains Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.52225/narra.v5i2.1578

Abstract

Colorectal cancer (CRC) is one of the leading causes of cancer-related mortality worldwide, necessitating the need for an effective therapeutic strategy. Beta vulgaris (beetroot) possesses active compounds that exert anti-cancer properties. The aim of this study was to evaluate the potential of beetroot as a preventative agent against the progression of CRC using differentially expressed gene (DEG) analysis and network pharmacology approaches. The protein-protein interaction network and molecular docking analyses were employed to assess the key interactions of beetroot active compounds with CRC-related target protein. Cytotoxicity of beetroot extract was experimentally evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide (MTT) assay on the HT29 cell line. The result of this study showed that protein in the cell cycle was significantly enriched in CRC, with cyclin-dependent kinase 4 (CDK4) gene as one of the specific genes. Quercetin, galangin, hesperidin, farrerol, and betanin were the most typical compounds of beetroot based on the Comparative Toxicogenomics Database (CTD). Molecular docking studies revealed the strong binding affinity between quercetin (-7.04 kcal/mol) and bentanin (-8.11 kcal/mol) with CDK4. Beetroot demonstrated anticancer properties against the HT29 cell line with IC50 value of 39.03±1.4 µg/mL. In conclusion, the beetroot extract has inhibitory activity against HT29 cell line proliferation, highlighting its potential in preventing the development of CRC through the substantial suppression of gene expression within the cell cycle pathway.
Co-Authors Adisti Dwijayanti Aryo Tedjo Berna Elya Erlina, Linda Fadilah Fadilah, Fadilah Fajrin, Ajeng M. Hashim, Najihah BM. Hashim, Najihah M. Kusmardi Kusmardi Ramadanti, Nur A. Rosmalena, Rosmalena Sri S. Ningsih, Sri S.