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7,7-双(3-吲哚基)-对甲酚,一种源自海洋细菌spp. DJA11的代谢产物,可抑制前列腺癌细胞的增殖和运动能力。

7,7-Bis(3-Indolyl)--Cresol, a Metabolite from Marine-Derived Bacterium spp. DJA11, Suppresses the Proliferation and Motility of Prostate Cancer Cells.

作者信息

Pulat Sultan, Lee Eun-Young, Choi Grace, Jung Yoon-Hee, Nam Sang-Jip, Kim Hangun

机构信息

College of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University, 255 Jungangno, Sunchon, Jeonnam 57922, Republic of Korea.

Department of Chemistry and Nanoscience, Ewha Womans University, Seoul 03760, Republic of Korea.

出版信息

J Microbiol Biotechnol. 2025 May 15;35:e2502035. doi: 10.4014/jmb.2502.02035.

DOI:10.4014/jmb.2502.02035
PMID:40374533
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12099627/
Abstract

Bacteria such as spp. in the marine environment can produce secondary metabolites which have significant potential applications in pharmaceuticals. In a study to discover bioactive secondary metabolites from marine spp., the strain DJA11 was encountered. HPLC/UV-guided isolation of the crude extract from this strain has led to the discovery of compound 1. Prostate cancer (PCa) is one of the biggest worldwide health issues because of its high diagnosis. CWR22Rv1 (22Rv1) is mutated in WT p53 and AR, C4-2 is derived from androgen-dependent human LNCaP and PC-3 is an androgen-independent cancer cell type. It was found that compound 1 exhibited no significant cytotoxicity at concentrations below 50 μM to human PCa cells, including 22Rv1, C4-2, and PC-3, like normal cell HEK293T. In addition, we presented that 1 inhibited the invasiveness and proliferation of 22Rv1, PC-3, and C4-2 cells by suppressing the activation of p-AKT, p-mTOR, p-STAT3, HSP90, and HSP70. Moreover, treatment with 1 decreased the mRNA expression level of ErbB4, PDK1, STAT3, HSP70, and HSP90 in some PCa cells. Therefore, compound 1 may have therapeutic potential in PCa due to its role in suppressing cancer proliferation and metastasis.

摘要

海洋环境中的某些细菌,如 spp.,能够产生具有重要药物应用潜力的次级代谢产物。在一项从海洋 spp. 中发现生物活性次级代谢产物的研究中,分离出了菌株 DJA11。通过高效液相色谱/紫外引导对该菌株的粗提物进行分离,发现了化合物 1。前列腺癌(PCa)因其高发病率成为全球最大的健康问题之一。CWR22Rv1(22Rv1)在野生型 p53 和雄激素受体(AR)中发生突变,C4-2 源自雄激素依赖的人 LNCaP,而 PC-3 是一种雄激素非依赖型癌细胞系。研究发现,化合物 1 在浓度低于 50 μM 时,对人前列腺癌细胞(包括 22Rv1、C4-2 和 PC-3)没有显著细胞毒性,对正常细胞 HEK293T 也是如此。此外,我们还发现化合物 1 通过抑制 p-AKT、p-mTOR、p-STAT3、HSP90 和 HSP70 的激活,抑制了 22Rv1、PC-3 和 C4-2 细胞的侵袭和增殖。而且,用化合物 1 处理后,一些前列腺癌细胞中 ErbB4、PDK1、STAT3、HSP70 和 HSP90 的 mRNA 表达水平降低。因此,化合物 1 可能因其在抑制癌症增殖和转移方面的作用而具有治疗前列腺癌的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63d2/12099627/de3fa83191b3/jmb-35-e2502035-f7.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63d2/12099627/de3fa83191b3/jmb-35-e2502035-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63d2/12099627/2a2ea04649c9/jmb-35-e2502035-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63d2/12099627/ee466c712dad/jmb-35-e2502035-f2.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63d2/12099627/de3fa83191b3/jmb-35-e2502035-f7.jpg

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