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研究揭示了从洛纳尔碱湖分离出的放线菌发酵代谢产物对HeLa癌细胞系的潜在细胞毒性活性。

Investigations Reveals Potential Cytotoxic Activity of Fermentation Metabolites from Actinomycetes Isolated from Lonar Soda Lake Against HeLa Cancer Cell Lines.

作者信息

Bawane Pradip, Yele Santosh

机构信息

SVKM's NMIMS, Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, Mumbai, Maharashtra- 400056, India.

Shri Vile Parle Kelavani Mandal's Institute of Pharmacy, Dhule, Maharashtra-424001, India.

出版信息

Curr Protein Pept Sci. 2025;26(5):378-391. doi: 10.2174/0113892037334392241216074545.

DOI:10.2174/0113892037334392241216074545
PMID:39791152
Abstract

BACKGROUND

Actinomycetes, Gram-positive bacteria, are recognized for producing bioactive metabolites. Lonar Soda Lake, an alkaline ecosystem, hosts diverse actinomycetes with possible anticancer activities.

AIM

To assess the cytotoxic potential of fermentation metabolites from actinomycetes isolated from Lonar Soda Lake against HeLa cancer cells employing and methods.

OBJECTIVES

Evaluate the cytotoxicity of fermentation metabolites from Lonar Lake actinomycetes on HeLa cells. Execute molecular docking to forecast metabolite connections with cancer-related proteins.

MATERIALS AND METHODS

The actinomycetes were isolated from the sediment sample of Lonar Lake using a selective medium and recognized by gene sequencing. Cytotoxicity on HeLa cells was assessed using the MTT assay, in consort with oxidative stress and apoptotic markers (GSH, MDA, TNF-α, and caspase 3). Molecular docking and molecular dynamics studies evaluated metabolite binding to cancer-related proteins (Bcl-2, TNF-α, caspase 3).

RESULTS

Fermentation metabolites of three Lonar Lake Sediment isolates (LLSD), LLSD-5, LLSD- 7, and LLSD-9 showing promising cytotoxic activity against HeLa cell lines by MTT assay, also significantly modulate the oxidative stress parameters (GSH, MDA), and cell apoptotic marker (TNF-α, caspase 3). IC values were 34.17 μM (LLSD-5), 53.85 μM (LLSD-7), and 69.54 μM (LLSD-9). Furthermore, molecular docking displayed robust binding affinities to cancer-related proteins, uncovering the possible mechanism of action.

CONCLUSION

The fermentation metabolites actinomycete isolates from Lonar Lake exhibit significant cytotoxic activity against HeLa cancer cell lines. Both and analyses support the potential of these metabolites as anticancer agents.

摘要

背景

放线菌是革兰氏阳性菌,以产生生物活性代谢产物而闻名。洛纳尔苏打湖是一个碱性生态系统,拥有多种可能具有抗癌活性的放线菌。

目的

采用[具体方法1]和[具体方法2]评估从洛纳尔苏打湖分离出的放线菌发酵代谢产物对宫颈癌细胞系的细胞毒性潜力。

目标

评估洛纳尔湖放线菌发酵代谢产物对宫颈癌细胞的细胞毒性。进行分子对接以预测代谢产物与癌症相关蛋白的结合情况。

材料与方法

使用选择性培养基从洛纳尔湖的沉积物样本中分离放线菌,并通过基因测序进行鉴定。采用MTT法评估对宫颈癌细胞的细胞毒性,并结合氧化应激和凋亡标志物(谷胱甘肽、丙二醛、肿瘤坏死因子-α和半胱天冬酶3)进行分析。分子对接和分子动力学研究评估代谢产物与癌症相关蛋白(Bcl-2、肿瘤坏死因子-α、半胱天冬酶3)的结合情况。

结果

洛纳尔湖沉积物分离株(LLSD)LLSD-5、LLSD-7和LLSD-9的发酵代谢产物通过MTT法显示出对宫颈癌细胞系有良好的细胞毒性活性,还显著调节氧化应激参数(谷胱甘肽、丙二醛)和细胞凋亡标志物(肿瘤坏死因子-α、半胱天冬酶3)。半数抑制浓度值分别为34.17 μM(LLSD-5)、53.85 μM(LLSD-7)和69.54 μM(LLSD-9)。此外,分子对接显示与癌症相关蛋白具有较强的结合亲和力,揭示了可能的作用机制。

结论

洛纳尔湖放线菌分离株的发酵代谢产物对宫颈癌细胞系具有显著的细胞毒性活性。[具体分析1]和[具体分析2]分析均支持这些代谢产物作为抗癌剂的潜力。

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本文引用的文献

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