Supernatant Metabolites from Halophilic Archaea to Reduce Tumorigenesis in Prostate Cancer In-vitro and In-vivo

Document Type: Research article

Authors

1 Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.

2 Department of Developmental Biology, Faculty of Basic Sciences and Advanced Technologies in Biology, University of Science and Culture, ACECR, Tehran, Iran.

3 Department of Molecular and Cellular Biology, Faculty of Basic Sciences and Advanced Technologies in Biology, University of Science and Culture, ACECR, Tehran, Iran.

4 dMicroorganisms Bank, Iranian Biological Resource Centre (IBRC), ACECR, Tehran, Iran.

5 Extremophiles Laboratory, Department of Microbiology, School of Biology and Center of Excellence in Phylogeny of Living Organisms, College of Science, University of Tehran, Tehran, Iran.

Abstract

Halophilic archaea are known as the novel producers of natural products and their supernatant metabolites could have cytotoxic effects on cancer cells. In the present study, we screened the anticancer potential of supernatant metabolites from eight native haloarchaeal strains obtained from a culture collection in Iran. Five human cancer cell lines including breast, lung, prostate and also human fibroblast cells as the normal control were used in the present study. Moreover, to evaluate the anti-tumor effect of the selected supernatant, inhibition of sphere formation and tumor development was assessed in-vitro and in-vivo, respectively. Among all strains, supernatant metabolites from Halobacterium salinarum IBRC M10715 had the most potent cytotoxic effect on prostate cancer cell lines (IC50 = 0.5 mg/mL) without any effects on normal cells. It significantly increased both early and late apoptosis (about 11% and 9%, respectively) in the androgen-dependent PC3 cell line, reduced sphere formation ability of DU145 and PC3 cells with down-regulation of SOX2 gene expression. Furthermore, our results revealed that tumors developed in nude mice significantly shrank post intratumor injection of metabolites of the haloarchaeal strain. In conclusion, we suggested here for the first time that supernatant metabolites from Halobacterium salinarum IBRC M10715 could be a novel component against prostate cancer in-vitro and in-vivo with remarkable reduction in stem-like properties of tumor.
 

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