Elya Berna, Rosmalena Rosmalena, Fajrin Ajeng M, Tedjo Aryo, Ramadanti Nur A, Azizah Norma N, Hashim Najihah Bm
Department of Pharmacognosy, Phytochemistry, and Natural Products, Faculty of Pharmacy, Universitas Indonesia, Jakarta, Indonesia.
Department of Medical Chemistry, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
Narra J. 2025 Apr;5(1):e1382. doi: 10.52225/narra.v5i1.1382. Epub 2025 Feb 10.
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 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 or Molecular docking simulations using Molegro Virtual Docker (MVD) were also performed to assess the potential inhibitory activity of metabolite compounds from stem against p53-regulating kinase (TP53RK. The results showed that the IC50 value of 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: or ( = 0.011), ( = 0.008), and ( = 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 stem might occur via pathways associated with cell senescence and cell cycle arrest. Molecular docking results of metabolite compounds from 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 () mRNA expression. In conclusion, the anti-proliferative effects of the ethanol extract from stem on breast cancer cells occurred by affecting cell cycle-related genes and inhibiting apoptosis protection mediated by overexpression of through p53 activity.
p53信号通路在调节细胞周期、细胞凋亡和衰老过程中起着关键作用，使其成为癌症研究中的一个关键靶点。本研究的目的是探讨[植物名称]茎部乙醇提取物对MCF-7乳腺癌细胞中p53通路相关基因增殖和表达的影响。为实现这一目标，采用实时定量PCR（RT-qPCR）来评估与细胞周期和衰老相关的下游基因的mRNA表达，包括[具体基因1]或[具体基因2]。还使用Molegro Virtual Docker（MVD）进行分子对接模拟，以评估[植物名称]茎部代谢产物化合物对p53调节激酶（TP53RK）的潜在抑制活性。结果表明，[植物名称]茎部乙醇提取物对MCF-7细胞的IC50值为38.27±0.72μg/mL。结果还显示，通过对mRNA表达的RT-qPCR分析观察到，与细胞衰老和细胞周期相关的下游基因的表达有所降低：[具体基因1]或[具体基因2]（P = 0.011）、[具体基因3]（P = 0.008）和[具体基因4]（P = 0.005）。这一事实表明，[植物名称]茎部乙醇提取物对增殖的抑制作用可能通过与细胞衰老和细胞周期停滞相关的途径发生。[植物名称]茎部代谢产物化合物的分子对接结果表明，角鲨烯（重排分数-112.70 kJ/mol）和钱币草素B（重排分数-110.68 kJ/mol）具有作为TP53RK抑制剂的潜力。分子动力学分析证实，与TP53RK的天然配体腺苷-亚氨基二磷酸（AMP-PNP）的重排分数相比，这些重排分数更小。这些计算机模拟结果通过[具体基因5]（[具体基因名称5]）mRNA表达的降低得到证实。总之，[植物名称]茎部乙醇提取物对乳腺癌细胞的抗增殖作用是通过影响细胞周期相关基因并抑制由p53活性介导的[具体基因6]过表达所介导的凋亡保护来实现的。
