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

Journal: Polymers
Published Date: Sep 19, 2018

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 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 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 . PBN11-8 possessed moderate cytotoxicity towards several cancer cell lines with IC 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.

Authors

  • Lanhong Zheng
    School of Pharmacy, Shanghai University of Medicine & Health Sciences, Shanghai 201318, China. zhenglanhong@126.com.
  • Xiangjie Zhu
    Key Laboratory of Sustainable Development of Polar Fishery, Ministry of Agriculture, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao 266071, China. zhuxiangjie1204@163.com.
  • Kangli Yang
    Key Laboratory of Sustainable Development of Polar Fishery, Ministry of Agriculture, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao 266071, China. hnysykl@163.com.
  • Meihong Zhu
    Key Laboratory of Sustainable Development of Polar Fishery, Ministry of Agriculture, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao 266071, China. zhumhlv@163.com.
  • Ammad Ahmad Farooqi
    Institute of Biomedical and genetic Engineering (IBGE), Islamabad, Pakistan.
  • Daole Kang
    Key Laboratory of Sustainable Development of Polar Fishery, Ministry of Agriculture, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao 266071, China. kdlqust@126.com.
  • Mi Sun
    Key Laboratory of Sustainable Development of Polar Fishery, Ministry of Agriculture, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao 266071, China. sunmi@ysfri.ac.cn.
  • Yixin Xu
    School of Pharmacy, Shanghai University of Medicine & Health Sciences, Shanghai 201318, China. xuyx@sumhs.edu.cn.
  • Xiukun Lin
    Department of Pharmacology, Southwest Medical University, Luzhou 646000, Sichuan, China. xiukunlin@126.com.
  • Yingang Feng
    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. fengyg@qibebt.ac.cn.
  • Fangfang Liang
    Key Laboratory of Sustainable Development of Polar Fishery, Ministry of Agriculture, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao 266071, China. liangfangfang12@163.com.
  • Fuming Zhang
    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. zhangf2@rpi.edu.
  • Robert J Linhardt
    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. linhar@rpi.edu.

Keywords

No keywords available for this article.

External Resources

Popular Topics
Recent Journals