7,7-Bis(3-Indolyl)- p -Cresol, a Metabolite from Marine-Derived Bacterium Vibrio spp. DJA11, Suppresses the Proliferation and Motility of Prostate Cancer Cells
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Bacteria such as Vibrio 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 Vibrio 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 cellHEK293T. 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.
Abstract
Bacteria such as Vibrio 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 Vibrio 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 cellHEK293T. 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.