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来自嗜盐栖热放线菌的细菌红素提取物可诱导髓系白血病细胞系发生凋亡并使细胞周期停滞。

Bacterioruberin extract from Haloferax mediterranei induces apoptosis and cell cycle arrest in myeloid leukaemia cell lines.

作者信息

Baeza-Morales Andrés, Pascual-García Sandra, Martínez-Peinado Pascual, Navarro-Sempere Alicia, Segovia Yolanda, Medina-García Miguel, Pujalte-Satorre Carolina, García María Magdalena, Martínez-Espinosa Rosa María, Sempere-Ortells José Miguel

机构信息

Department of Biotechnology, University of Alicante, Carretera San Vicente del Raspeig s/n, San Vicente del Raspeig, Alicante, 03690, Spain.

Multidisciplinary Institute for Environmental Studies "Ramón Margalef" (IMEM), University of Alicante, Carretera San Vicente del Raspeig s/n, San Vicente del Raspeig, Alicante, 03690, Spain.

出版信息

Sci Rep. 2025 Jul 2;15(1):23485. doi: 10.1038/s41598-025-06999-3.

Abstract

Carotenoids, a diverse group of naturally occurring pigments, have gained attention for their potential anticancer properties. Among them, bacterioruberin (BR), a rare C50 carotenoid, has shown promising bioactivities. This study evaluates the antiproliferative and cytotoxic effects of a bacterioruberin-rich carotenoid extract (BRCE) derived from Haloferax (H.) mediterranei on myeloid leukaemia (ML) cell lines, including chronic myelogenous leukaemia (CML) and acute myelogenous leukaemia (AML) models. Using MTT assay, Annexin V/PI and AO/EtBr staining, CFDA-SE proliferation assay, PI-based cell cycle analysis, and HDCF-DA for reactive oxygen species (ROS) quantification, we demonstrate that BRCE significantly reduces cell viability, induces apoptosis, causes G2/M cell cycle arrest, and increases ROS levels in leukaemia cell lines. Notably, BRCE exhibited selective cytotoxicity, with minimal effects on normal PBMCs from healthy donors, suggesting its potential for tumour-specific targeting. Additionally, we analysed the morphological features of the cells treated with BRCE, observing significant changes such as cell blebbing, clumping, and the formation of apoptotic bodies, which are indicative of the induction of apoptosis. Overall, this research underscores an antitumoural therapeutic potential of BRCEs from H. mediterranei, providing a basis for future studies on their application in leukaemia treatment. Further investigation is needed to fully understand the molecular mechanisms involved and optimize BRCE for clinical use.

摘要

类胡萝卜素是一类多样的天然色素,因其潜在的抗癌特性而受到关注。其中,细菌红素(BR)是一种罕见的C50类胡萝卜素,已显示出有前景的生物活性。本研究评估了源自地中海嗜盐菌(H. mediterranei)的富含细菌红素的类胡萝卜素提取物(BRCE)对髓系白血病(ML)细胞系的抗增殖和细胞毒性作用,包括慢性粒细胞白血病(CML)和急性髓系白血病(AML)模型。通过MTT法、Annexin V/PI和AO/EtBr染色、CFDA-SE增殖分析、基于PI的细胞周期分析以及用于活性氧(ROS)定量的HDCF-DA,我们证明BRCE显著降低细胞活力、诱导凋亡、导致G2/M期细胞周期阻滞,并增加白血病细胞系中的ROS水平。值得注意的是,BRCE表现出选择性细胞毒性,对健康供体的正常外周血单核细胞(PBMC)影响最小,表明其具有肿瘤特异性靶向的潜力。此外,我们分析了用BRCE处理的细胞的形态特征,观察到明显变化,如细胞起泡、聚集和凋亡小体的形成,这些均表明凋亡的诱导。总体而言,本研究强调了地中海嗜盐菌BRCE的抗肿瘤治疗潜力,为其在白血病治疗中的应用的未来研究提供了基础。需要进一步研究以充分了解其中涉及的分子机制并优化BRCE用于临床。

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