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2.
Polymers (Basel) ; 10(9)2018 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-30960968

RESUMO

The development of antitumor drugs has attracted cancer researchers and the identification of novel antitumor lead compounds is certainly of great interest. The fermentation broth of Bacillus sp. N11-8, which was isolated from the Antarctic waters, showed cytotoxicity towards different cells. A cytotoxic polypeptide, PBN11-8, was purified from the fermentation broth of Bacillus sp. N11-8 using ultrafiltration, ammonium sulfate precipitation, anion exchange liquid chromatography and high performance liquid chromatography (HPLC). Cloning and sequence analysis showed that PBN11-8 polypeptide (MW: ~19 kDa by the electrospray-ionization (ESI)) displayed high similarity with peptidase M84 from Bacillus pumilus. PBN11-8 possessed moderate cytotoxicity towards several cancer cell lines with IC50 values of 1.56, 1.80, 1.57, and 1.73 µg/mL against human hepatocellular carcinoma cell line BEL-7402, human renal clear cell adenocarcinoma cell line 786-0, human hepatocellular carcinoma cell line HepG2, and human pancreatic cancer cell line Panc-28, respectively. Moreover, the polypeptide displayed weak cytotoxicity towards normal cell line renal tubular epithelial cell line HK2 and human normal liver cell line L02 cells. Wound healing migration and Transwell experiments demonstrate that PBN11-8 could inhibit the migration and invasion of BEL-7402. Further investigation revealed that PBN11-8 suppresses focal adhesion kinase (FAK)-mediated adhesion, migration, and invasion by disturbing FAK/extracellular regulated protein kinases (ERK) signaling and matrix metalloproteinase-2(MMP-2) and matrix metalloproteinase-9 (MMP-9) in BEL-7402 cells. Thus, PBN11-8 represents a potential novel anti-cancer lead compound.

3.
Food Sci Nutr ; 4(2): 198-206, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27004109

RESUMO

The Antarctic is a potentially important library of microbial resources and new bioactive substances. In this study, microorganisms were isolated from surface water samples collected from different sites of the Antarctic. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay-based cytotoxicity-tracking method was used to identify Antarctic marine microorganism resources for antitumor lead compounds. The results showed that a total of 129 Antarctic microorganism strains were isolated. Twelve strains showed potent cytotoxic activities, among which a Gram-negative, rod-shaped bacterium, designated as N11-8 was further studied. Phylogenetic analysis based on 16S rRNA gene sequence showed that N11-8 belongs to the genus Bacillus. Fermented active products of N11-8 with molecular weights of 1-30 kDa had higher inhibitory effects on different cancaer cells, such as BEL-7402 human hepatocellular carcinoma cells, U251 human glioma cells, RKO human colon carcinoma cells, A549 human lung carcinoma cells, and MCF-7 human breast carcinoma cells. However, they displayed lower cytotoxicity against HFL1 human normal fibroblast lung cells. However, they displayed lower cytotoxicity against HFL1 human normal fibroblast lung cells. Microscopic observations showed that the fermented active products have inhibitory activity on BEL-7402 cells similar to that of mitomycin C. Further studies indicated that the fermented active products have high pH and high thermal stability. In conclusion, most strains isolated in this study may be developed as promising sources for the discovery of antitumor bioactive substances. The fermented active products of Antarctic marine Bacillus sp. N11- 8 are expected to be applied in the prevention and treatment of cancer.

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