Essential oil from Ocimum carnosum induces ROS mediated mitochondrial dysfunction and intrinsic apoptosis in HL-60 cells

IF 2.6 3区 医学 Q3 TOXICOLOGY Toxicology in Vitro Pub Date : 2024-12-07 DOI:10.1016/j.tiv.2024.105988
Madhunika Agrawal , A.K. Saxena , Satyam Kumar Agrawal
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Abstract

The present study demonstrates that essential oil from Ocimum carnosum (EOC), possesses potent cytotoxic properties against human promyelocytic leukemia HL-60 cells. The results demonstrated a concentration- and time-dependent reduction in cell viability, with an IC50 value of 0.029 μl/ml after 24 h. Further mechanistic studies revealed that EOC induces apoptosis, a regulated form of cell death in HL-60 cells. This was evidenced by morphological changes characteristic of apoptosis, including cell shrinkage, membrane blebbing, and nuclear condensation. Additionally, flow cytometric analysis demonstrated a significant increase in the sub-G0 cell population, indicative of DNA fragmentation. The mitochondrial pathway of apoptosis appears to be involved in EOC-induced cell death. A loss of mitochondrial membrane potential and the subsequent release of cytochrome c into the cytosol were observed. Pronounced quantity of cytosolic cytochrome c was associated with Bcl-2 depletion. Moreover, cytochrome c, in conjunction with other apoptotic factors, activates caspases, a family of cysteine proteases that execute cell death. These findings collectively indicate that EOC possesses promising anti-cancer properties through the induction of apoptosis via a mitochondrial-dependent pathway. However, further studies are required to elucidate the precise molecular mechanisms underlying EOC's cytotoxic effects and to evaluate its therapeutic potential in vivo.

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鹿茸精油诱导ROS介导的HL-60细胞线粒体功能障碍和内在凋亡。
本研究表明,鹿茸精油对人早幼粒细胞白血病HL-60细胞具有有效的细胞毒性。结果表明,细胞活力的降低与浓度和时间有关,24 h后的IC50值为0.029 μl/ml。进一步的机制研究表明,EOC诱导HL-60细胞凋亡,这是一种受调节的细胞死亡形式。细胞凋亡的形态学改变,包括细胞收缩、膜起泡和核凝聚,证明了这一点。此外,流式细胞术分析显示亚g0细胞群显著增加,表明DNA片段化。线粒体凋亡途径似乎参与了eoc诱导的细胞死亡。观察到线粒体膜电位丧失,随后细胞色素c释放到细胞质中。胞质细胞色素c的显著量与Bcl-2的缺失有关。此外,细胞色素c与其他凋亡因子一起激活半胱天冬酶,这是一种执行细胞死亡的半胱氨酸蛋白酶家族。这些发现共同表明,EOC通过线粒体依赖途径诱导细胞凋亡,具有良好的抗癌特性。然而,需要进一步的研究来阐明EOC细胞毒性作用的确切分子机制,并评估其体内治疗潜力。
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来源期刊
Toxicology in Vitro
Toxicology in Vitro 医学-毒理学
CiteScore
6.50
自引率
3.10%
发文量
181
审稿时长
65 days
期刊介绍: Toxicology in Vitro publishes original research papers and reviews on the application and use of in vitro systems for assessing or predicting the toxic effects of chemicals and elucidating their mechanisms of action. These in vitro techniques include utilizing cell or tissue cultures, isolated cells, tissue slices, subcellular fractions, transgenic cell cultures, and cells from transgenic organisms, as well as in silico modelling. The Journal will focus on investigations that involve the development and validation of new in vitro methods, e.g. for prediction of toxic effects based on traditional and in silico modelling; on the use of methods in high-throughput toxicology and pharmacology; elucidation of mechanisms of toxic action; the application of genomics, transcriptomics and proteomics in toxicology, as well as on comparative studies that characterise the relationship between in vitro and in vivo findings. The Journal strongly encourages the submission of manuscripts that focus on the development of in vitro methods, their practical applications and regulatory use (e.g. in the areas of food components cosmetics, pharmaceuticals, pesticides, and industrial chemicals). Toxicology in Vitro discourages papers that record reporting on toxicological effects from materials, such as plant extracts or herbal medicines, that have not been chemically characterized.
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