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PBN11-8, a Cytotoxic Polypeptide Purified from Marine Bacillus, Suppresses Invasion and Migration of Human Hepatocellular Carcinoma Cells by Targeting Focal Adhesion Kinase Pathways

1
School of Pharmacy, Shanghai University of Medicine & Health Sciences, Shanghai 201318, China
2
Key Laboratory of Sustainable Development of Polar Fishery, Ministry of Agriculture, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao 266071, China
3
Shanghai Ocean University, Shanghai 201306, China
4
Institute of Biomedical and Genetic Engineering (IBGE), Islamabad 44000, Pakistan
5
Department of Pharmacology, Southwest Medical University, Luzhou 646000, Sichuan, China
6
Shandong Provincial Key Laboratory of Energy Genetics and Qingdao Engineering Laboratory of Single Cell Oil, Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, 189 Songling Road, Qingdao 266101, China
7
Departments of Chemistry and Chemical Biology, Chemical and Biological Engineering, Biology and Biomedical Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Polymers 2018, 10(9), 1043; https://doi.org/10.3390/polym10091043
Received: 12 March 2018 / Revised: 20 April 2018 / Accepted: 2 May 2018 / Published: 19 September 2018
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. View Full-Text
Keywords: polypeptide; cytotoxicity; FAK; invasion polypeptide; cytotoxicity; FAK; invasion
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MDPI and ACS Style

Zheng, L.; Zhu, X.; Yang, K.; Zhu, M.; Farooqi, A.A.; Kang, D.; Sun, M.; Xu, Y.; Lin, X.; Feng, Y.; Liang, F.; Zhang, F.; Linhardt, R.J. PBN11-8, a Cytotoxic Polypeptide Purified from Marine Bacillus, Suppresses Invasion and Migration of Human Hepatocellular Carcinoma Cells by Targeting Focal Adhesion Kinase Pathways. Polymers 2018, 10, 1043.

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