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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. [ABSTRACT FROM AUTHOR]

In a drug discovery process from halophiles, Salinivenus iranica crude metabolites showed a great cytotoxic activity against breast cancer cell lines including MCF-7, MDA-MB-468, and MDA-MB-231. HPLC analysis and downstream MTT assays were done to purify the active component of the S. iranica metabolites. Moreover, FT-IR and LC-MS analysis were done to structural detection of the effector molecule of the selected metabolite. To find the effective molecule in S. iranica supernatant metabolite, the metabolite was fractionated into 31 fractions by four solvents: hexane, ethyl acetate, water, and butanol. The viability of human breast cancer cells was assayed in the presence of each fraction with the concentration of 100 ng/mL. The results showed that fraction number 6 of hexane had reduced the viability of all cell lines to 1% while the other 30 fractions had no significant effect on cell lines viability. The mass spectrophotometry determined that molecular weight (MW) of this fraction was about 1961.78 Da. In FT-IR analysis, three types of functional molecules were found in hexane fraction number 6. In 2950 - 2850 cm-1, Alkyl C-H Stretch was detected which are usually less useful in determining structure because of fairly ubiquitination. In 3500 - 3300 cm-1, Amine N-H Stretch was detected which is a primary amine, as primary amines produce two N-H stretch absorptions, secondary amides only one, and tertiary none. In 3550 - 3200 cm-1, Alcohol/Phenol O-H Stretch was detected. In conclusion, based on its unique features, the active competent of S. iranica metabolite could be a novel component against breast cancer and additional studies and full characterization of this effector molecule could result in a new drug with strong anti-cancer stem cell effects on breast cancer. [ABSTRACT FROM AUTHOR]

Their ability to live in salt concentrations makes halophiles a good choice for a search for novel bioactive natural components with different medicinal applications. The role of metabolites from haloarchaeal strains belonging to different groups for application in cancer treatment is not well studied (Hou & Cui, 2018). A total of eight haloarchaeal metabolites have been evaluated for their anticancer potential against five human cancer cell lines of breast, lung and prostate cancers, while using a fibroblast cell line as a control. Downstream analysis including sphere and colony formation assay, invasion and migration assays, real-time PCR analysis, cell cycle, apoptosis assays and in vivo experiments were done to find the most potent metabolite with efficient anti-cancer activity. All archaeal metabolites investigated were found to be cytotoxic against one or more cancer cell lines and/or normal cells after 48 h with cell line specific activity. A metabolite from one strain has a potent cytotoxic effect on Du-145 and PC3 cell lines with an IC50 of 500 µg/ml without any effects on normal cells, and reduced sphere and colony formation ability of DU145 and PC3 cells with down-regulation of SOX2 gene expression. This metabolite affected the invasion and migration ability of these cell lines. It significantly increased both early and late apoptosis in the androgen-dependent PC3 cell line and caused tumor shrinkage in human prostate tumors in nude mice. The results of the present study indicated a major anti-cancer effect of metabolites derived from haloarchaeal strains. [ABSTRACT FROM AUTHOR]

[This corrects the article on p. 840 in vol. 16, PMID: 28827999.].

Halophilic prokaryotes are extremophile microorganisms that grow optimally in media containing salts and almost appeared pigmented. Many of them contain high concentrations of carotenoids. Amongst 15 strains of halophilic prokaryotes isolated from industrial tannery wastewater in Qom, a Gram-stain-positive coccoid, aerobic, non-endospore-forming, halotolerant bacterium designated as strain QWT-12 showed high capacity in the production of carotenoids in a wide range of culture medium factors. 16S rRNA gene analysis showed that this strain belongs to the genus Kocuria . Carotenoids from this strain were extracted by methanol. MTT assay for extracted carotenoid was carried out against seven cancer cell lines belonging to breast, lung and prostate cancer with negative control of fibroblast cell line through six concentration levels to find out IC 50 . Based on statistical analysis of data from MTT assay, IC 50 of 1, 4 and 8 mg/ml for MCF-7, (A549 and MDA-MB-468) and MDA-MB-231 respectively. Additionally, qualitative carotenoid determination was carried out using spectrophotometric method in 300-600 nm and thin layer chromatography, respectively. According to the obtained results from mass spectrophotometry, absorption spectrum of strain QWT-12 is similar to the absorption spectrum of the carotenoid neurosporene.