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All Journal HAYATI Journal of Biosciences Torani Journal of Fisheries and Marine Science Media Penelitian dan Pengembangan Kesehatan Jurnal Fitofarmaka Indonesia Indonesian Journal of Chemistry ANNALES BOGORIENSES Dinamisia: Jurnal Pengabdian Kepada Masyarakat Majalah Farmasi dan Farmakologi (Trends in Pharmacy and Pharmaceutical Sciences) JSFK (Jurnal Sains Farmasi & Klinis) FITOFARMAKA: Jurnal Ilmiah Farmasi PengabdianMu: Jurnal Ilmiah Pengabdian kepada Masyarakat JFIOnline Jurnal Ilmu Kefarmasian Indonesia Jurnal Mandala Pharmacon Indonesia Jurnal Riset Kesehatan Poltekkes Depkes Bandung Sainstech Farma: Jurnal Ilmu Kefarmasian Narra J Jurnal Ilmiah Kesehatan (JIKA) Pharmaceutical Sciences and Research (PSR) Makara Journal of Science Journal of Pharmaceuticals and Natural Sciences Jurnal Kefarmasian Indonesia Annales Bogorienses
Berna Elya
Fakultas Farmasi Universitas Indonesia
Agriculture, Biological Sciences & Forestry Biochemistry, Genetics & Molecular Biology Chemical Engineering, Chemistry & Bioengineering Chemistry Decision Sciences, Operations Research & Management Dentistry Earth & Planetary Sciences Economics, Econometrics & Finance Environmental Science Health Professions Immunology & microbiology Law, Crime, Criminology & Criminal Justice Medicine & Pharmacology Nursing Public Health Social Sciences Other

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Journal : Narra J

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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.
Co-Authors . Azizahwati . Azizahwati . Farida . Frengki . Katrin . Katrin . Nofiantini Ali Muhammad Shodiq Amarila Malik Anastasia Bangun Anastasia Bangun, Anastasia Ariestanti, Donna Maretta Arifayu Addiena Kurniatri Arifayu Addiena Kurniatri Arifianti, Ayun Erwina Aryo Tedjo Atiek Soemiati Atiek Soemiati Atiek Soemiati Atriyon Julzarika Atriyon Julzarika Azizah, Norma N. Azizahwati Azizahwati Azminah Azminah Basah, Katrin Chairunissa, Ananda Hanny Charissa, Meiliana Daan Khambri Dadang Kusmana Dadang Kusmana Deddi Prima Donna Maretta Ariestanti Effionora Anwar Elis Apriyanti Elis Apriyanti, Elis Emiyanah . Emiyanah, Emiyanah Fadlina Chany Saputri Fajriati, Annisa Fajrin, Ajeng M. Farida Farida Farida Ibrahim Fasya Hadaina Maharani Fatma Sri Wahyuni Febriani, Amelia Febrina Amelia Saputri Forestrania, Roshamur Cahya Forestrania, Roshamur Cahyan Frengki Frengki Fulka Nurzaman Hanita Omar Hashim, Najihah BM. Hayun Hayun Henny Vanda Herman Suryadi Hessy Novita Hindun Wilda Risni Iis Irawatty Dewi Ika Maruya Kusuma Ika Mustika Imam Syafi'i Irianti, Marina Ika Islamudin Ahmad Jamilah Abbas Jamilah Abbas Jantan, Ibrahim Joshita Djajadisastra Joshita Djajadisastra Joshita Djajadisastra, Joshita Juheini Amin Juheini Amin Juheini Amin Julian, Muhamad Iqbal Kamaruzzaman, Mohd Amir Kartika Citra Dewi Permata Sari Katrin Basah Katrin Katrin Krinalawaty, Nevy Kusmardi Kusmardi Ladeska, Vera Liza Ariantina Maharani Maharani, Maharani Maharani, Fasya Hadaina Mahdi Jufri Mahmuda, Nur Amalia Makau, Juliann Nzembi Marcha Putri, Nada MARIA BINTANG Martha, Septiani Media Fitri Isma Nugraha Meiliana Charissa Mia Permawati Mihardja, Laurentia K. Muh Alias L Rajamuddin Muhamad Iqbal Julian MUHAMMAD HANAFI Muhammad Hanafi Muhammad Hanafi Muhammad Hanafi Muhammad Muhammad Nanang Yunarto Nanang Yunarto Neneng Siti Silfi Ambarwati Nevy Krinalawaty Nisa Maria Nofiantini Nofiantini Nofiantini Nofiantini, Nofiantini Noni Zakiah Novi Fajar Utami Novi Sulistyaningrum Novita, Hessy Nugraha, Media Fitri Isma Nurzaman, Fulka Prasetio, Nisrina Putri Puspitasari, Rara Merinda Rahmadi, Agus Rahmasari, Ratika Rajamuddin, Muh Alias Rajamuddin, Muh Alias L Ramadanti, Nur A. Rani Sauriasari, Rani Ratu Ayu Dewi Sartika Reflinur Reflinur REFLINUR REFLINUR Regita Putri, Jasmine Retnosari Andrajati Rieka Widihasputri Rieka Widihasputri, Rieka Robiatul Adawiyah Rohmat, Siti Saudah Rosmalena, Rosmalena Rossa Yunita ROSSA YUNITA Santy Rahmawati Sari, Atika Mutiara Sari, Rifta Sintiami Ramadhani Siti Khadijah Soleh Kosela Soleh Kosela Syafi'i, Imam Syamsu Nur, Syamsu Taufiq Indra Rukmana Veryanti, Putu Rika Wening Enggarini Wening Enggarini Winnugroho Wiratman, Manfaluthy Hakim, Tiara Aninditha, Aru W. Sudoyo, Joedo Prihartono Yesi Desmiaty, Yesi Yuditya Artha