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8-羟基喹啉,一种来自链霉菌属的天然螯合剂,通过BCL2/STAT3调节途径抑制A549肺癌细胞系。

8-Hydroxyquinoline a natural chelating agent from Streptomyces spp. inhibits A549 lung cancer cell lines via BCL2/STAT3 regulating pathways.

作者信息

Balthazar Joseph Devadass, Soosaimanickam Maria Packiam, Emmanuel C, Krishnaraj Thirugnansambantham, Sheikh Abdullah, Alghafis Saleh Fahad, Ibrahim Hairul-Islam Mohamed

机构信息

Division of Microbiology and Biotechnology, Entomology Research Institute, Loyola College, Chennai, Tamil Nadu, 600 034, India.

PG and Research Department of Advanced Zoology and Biotechnology, Loyola College, Chennai, Tamil Nadu, 600 034, India.

出版信息

World J Microbiol Biotechnol. 2022 Aug 12;38(10):182. doi: 10.1007/s11274-022-03368-4.

Abstract

Biomolecules from Streptomyces spp. are emerging sources of natural drugs and have been focused on over the decade. The discovery of bioactive chemotherapeutic molecules from soil Streptomyces spp. has opened the medium for the search for natural drugs. In the current study, 8-HOQ was extracted and purified from soil Streptomyces spp. and was evaluated on A549 and BEAS cell lines. The apoptotic and caspase mediated pathways were evaluated using cell proliferation, dual fluorescent staining, migration, invasion and mRNA as well as protein quantification of apoptotic markers. In vitro cytotoxicity test revealed that 8-HOQ possesses potent cytotoxicity activities with IC values of 26 µM, 5 µM, 7.2 µM at 24 h, 48 h, and 72 h respectively against A549 lung cancer cell lines. The result also demonstrated that 8-HOQ from Streptomyces spp significantly inhibited the A549 lung cancer cell lines and activated the intrinsic pathways of apoptosis. The caspase-3 and caspase-8 activities were potentially elevated in 8-HOQ treated A549 cell lines and confirmed that 8-HOQ mediated A549 cancer cell death through the intrinsic pathway. The results explored caspase-mediated apoptosis as a mechanism underlying the inhibition of cancer cell viability in a dose-dependent manner. The expression of P53, BCL2 and STAT3 were inhibited in A549 cell lines and confirmed the metastasis inhibitory potential of 8-HOQ by blocking migration and invasion in A549 cell lines. These results indicated that 8-HOQ from Streptomyces spp. potentially inhibited growth and migration of A549 lung cancer cell lines.

摘要

来自链霉菌属的生物分子是天然药物的新兴来源,并且在过去十年中一直受到关注。从土壤链霉菌属中发现具有生物活性的化疗分子为天然药物的寻找开辟了道路。在当前的研究中,从土壤链霉菌属中提取并纯化了8-羟基喹啉,并在A549和BEAS细胞系上进行了评估。使用细胞增殖、双荧光染色、迁移、侵袭以及凋亡标志物的mRNA和蛋白质定量来评估凋亡和半胱天冬酶介导的途径。体外细胞毒性试验表明,8-羟基喹啉具有强大的细胞毒性活性,在24小时、48小时和72小时时对A549肺癌细胞系的IC值分别为26 μM、5 μM、7.2 μM。结果还表明,来自链霉菌属的8-羟基喹啉显著抑制A549肺癌细胞系并激活凋亡的内在途径。在经8-羟基喹啉处理的A549细胞系中,半胱天冬酶-3和半胱天冬酶-8的活性可能升高,这证实了8-羟基喹啉通过内在途径介导A549癌细胞死亡。结果探索了半胱天冬酶介导的凋亡是以剂量依赖性方式抑制癌细胞活力的潜在机制。在A549细胞系中,P53、BCL2和STAT3的表达受到抑制,并通过阻断A549细胞系中的迁移和侵袭证实了8-羟基喹啉的转移抑制潜力。这些结果表明,来自链霉菌属的8-羟基喹啉可能抑制A549肺癌细胞系的生长和迁移。

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