Abstract
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.
Highlights
The worldwide incidence of cancer increases year by year due to environmental pollution and aging
BEL-7402 cells treated with 4.0 μg/mL PBN11-8 (Figure 6a,b). These results indicate that PBN11-8 inhibits the the activation activationof ofERK
We found that PBN11-8 could reduce the expression of integrin, focal adhesion kinase (FAK), and p-FAK in protein levels. qRT-Polymerase Chain Reaction (PCR) results showed that the mRNA level of integrin and FAK was decreased in BEL-7402 cells treated with the anticancer protein
Summary
The worldwide incidence of cancer increases year by year due to environmental pollution and aging. It is of great significance to discover and study new anti-tumor drugs. The oceans, accounting for about three-quarters of the earth’s surface, contain extremely diverse resources [1], including aquatic species and various microbes. Marine microbes are an important source of new drugs and functional foods. These microbes produce large numbers of unusual natural compounds with unique structures and physiological activities required for their growth and metabolism in an extremely adverse living environment (i.e., high salt, high pressure, lack of oxygen, lack of sunlight). The most dominant marine microbes, marine bacteria, produce a wide variety of novel bioactive substances and have become an important resource in new drug screening
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