PBN11-8, a cytotoxic polypeptide purified from marine Bacillus, suppresses invasion of human hepatocellular carcinoma cells by targeting focal adhesion kinase pathways
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Authors
Zheng, Lanhong
Zhu, Xiangjie
Yang, Kangli
Zhu, Meihong
Farooqi, Ammad Ahmad
Kang, Daole
Sun, Mi
Xu, Yixin
Lin, Xiukun
Feng, Yingang
Issue Date
2021-01-01
Type
Article
Language
ENG
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
Alternative Title
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.
Description
Polymers, 10, 1043
Erratum: Polymers 2021, 13
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Erratum: Polymers 2021, 13
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Full Citation
PBN11-8, a cytotoxic polypeptide purified from marine Bacillus, suppresses invasion of human hepatocellular carcinoma cells by targeting focal adhesion kinase pathways, K. Yang, X. Zhu, M. Zhu, X. Lin, D. Kang, M. Sun, Y. Feng, F. Liang, F. Zhang, R. J. Linhardt, L. Zheng, Polymers, 10, 1043, 2018. Erratum: Polymers 2021, 13.
Publisher
Multidisciplinary Digital Publishing Institute (MDPI)
Terms of Use
Journal
Volume
Issue
PubMed ID
DOI
ISSN
20734360