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从SiHa宫颈癌细胞中分离出的生物碱刺桐碱诱导的凋亡和G2/M期细胞周期阻滞

Apoptosis and G2/M Phase Cell Cycle Arrest Induced by Alkaloid Erythraline Isolated from in SiHa Cervical Cancer Cell.

作者信息

Miranda Cleine Aglacy Nunes, Souza Amaxsell Thiago Barros de, Soares Ana Katarina Menezes da Cruz, Bernardes-Oliveira Emanuelly, Rocha Hugo Alexandre Oliveira, Barbosa Euzébio Guimarães, Guaratini Thais, Lucena-Silva Norma, Cobucci Ricardo Ney, Giordani Raquel Brandt, Crispim Janaina Cristiana de Oliveira

机构信息

Postgraduate Program in Development and Technological Innovation in Medicines, Federal University of Rio Grande do Norte, Natal 52171-900, RN, Brazil.

Postgraduate Program in Sciences Applied to Women's Health, Federal University of Rio Grande do Norte, Natal 59012-310, RN, Brazil.

出版信息

Int J Mol Sci. 2025 May 12;26(10):4627. doi: 10.3390/ijms26104627.

Abstract

Cervical cancer remains a significant global health concern, causing more than 300,000 deaths annually. , a tree native to north-eastern Brazil, contains bioactive alkaloids with potential anticancer properties. This study aimed to characterize the alkaloid-enriched fraction of leaves and investigate the effects of the alkaloid erythraline on apoptosis and cell cycle in SiHa cervical cancer cells. Using Gas Chromatography-Mass Spectrometry (GC-MS), six alkaloids, including erythraline, were identified. Cytotoxicity was assessed through proliferation assays on SiHa cells and peripheral blood mononuclear cells (PBMCs). Apoptosis and cell cycle analyses were performed using flow cytometry, and in silico virtual screening identified potential protein targets of erythraline. Erythraline showed time- and concentration-dependent inhibitory effects on SiHa cell proliferation, with significant cytotoxicity observed at 50 µg/mL. Morphological changes, chromatin condensation, and increased apoptotic cell percentages confirmed the induction of caspase-independent apoptosis. Erythraline also induced G2/M cell cycle arrest, with 22% of cells in the G2/M phase compared with 7.25% in the untreated controls. In silico analysis identified polyamine oxidase, pyruvate kinase M2, and tankyrase as potential targets that contribute to the antitumor activity of erythraline. These findings suggest that erythraline is a promising candidate for anticancer therapy, warranting further investigation.

摘要

宫颈癌仍然是一个重大的全球健康问题,每年导致超过30万例死亡。巴西东北部本土的一种树,含有具有潜在抗癌特性的生物活性生物碱。本研究旨在表征该树树叶中富含生物碱的部分,并研究生物碱刺桐灵对SiHa宫颈癌细胞凋亡和细胞周期的影响。使用气相色谱 - 质谱联用仪(GC-MS)鉴定出包括刺桐灵在内的六种生物碱。通过对SiHa细胞和外周血单个核细胞(PBMC)进行增殖测定来评估细胞毒性。使用流式细胞术进行凋亡和细胞周期分析,并且计算机虚拟筛选确定了刺桐灵的潜在蛋白质靶点。刺桐灵对SiHa细胞增殖表现出时间和浓度依赖性抑制作用,在50μg/mL时观察到显著的细胞毒性。形态学变化、染色质浓缩以及凋亡细胞百分比增加证实了非半胱天冬酶依赖性凋亡的诱导。刺桐灵还诱导G2/M期细胞周期停滞,22%的细胞处于G2/M期,而未处理对照组为7.25%。计算机分析确定多胺氧化酶、丙酮酸激酶M2和端锚聚合酶为有助于刺桐灵抗肿瘤活性的潜在靶点。这些发现表明刺桐灵是一种有前途的抗癌治疗候选物,值得进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbab/12111132/ead2140824c6/ijms-26-04627-g001.jpg

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