Induction of programmed cell death in lung cancer cells by secondary metabolites of Nocardia carnea UTMC 863 as soil actinomycetes

Tohid Moradi Gardeshi, Rahil Norbakhsh, Soheila Khaksari, Zahra Boroughani
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Abstract

Background: Apoptosis induction is one of the effective mechanisms in cancer therapy. So far, various natural sources have been identified for inducing apoptosis in cancer cells. This study proposed identifying promising active drug pharmacophores of soil actinomycetes with the capability of apoptosis induction in A549 cells, a human alveolar adenocarcinoma cell line. Methods: The crude extract of Nocardia carnea UTMC 863 was obtained from UTBC (University of Tehran Biocompound Collection). After 48 hours of exposure, cell viability, gene expression, and apoptosis rate were determined using MTT, quantitative real-time-PCR, and flow cytometry. Results: The MTT assay exhibited that the effective concentrations of UTMC863 and doxorubicin (positive control) were 24 µg/ml and 1 µM, respectively. UTMC 863 with a 24 µg/ml concentration and doxorubicin could induce apoptosis in the A549 cell line. Also, apoptosis-related gene expression increased in the UTMC863 group compared to the untreated group (p<0.01). Conclusions: The crude extract of Nocardia carnea UTMC 863 can induce apoptosis in A549 cells, and it may be one of the promising pharmacophores for cancer therapy.
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诺卡菌UTMC 863次生代谢产物作为土壤放线菌诱导肺癌细胞程序性死亡
背景:细胞凋亡诱导是肿瘤治疗的有效机制之一。到目前为止,已经发现了多种天然来源的诱导癌细胞凋亡。本研究提出在人肺泡腺癌细胞A549细胞中寻找具有诱导凋亡能力的土壤放线菌活性药物载体。方法:从德黑兰大学生物化合物库中提取诺卡迪亚菌UTMC 863粗提物。暴露48小时后,采用MTT、实时荧光定量pcr和流式细胞术检测细胞活力、基因表达和凋亡率。结果:MTT法显示,UTMC863和阿霉素(阳性对照)的有效浓度分别为24µg/ml和1µM。24µg/ml浓度的UTMC 863和阿霉素可诱导A549细胞株凋亡。与未治疗组相比,UTMC863组细胞凋亡相关基因表达增加(p<0.01)。结论:诺卡菌UTMC 863粗提物具有诱导A549细胞凋亡的作用,可能是一种很有前景的抗癌药物载体。
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