PMID- 30960968 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20210120 IS - 2073-4360 (Electronic) IS - 2073-4360 (Linking) VI - 10 IP - 9 DP - 2018 Sep 19 TI - PBN11-8, a Cytotoxic Polypeptide Purified from Marine Bacillus, Suppresses Invasion and Migration of Human Hepatocellular Carcinoma Cells by Targeting Focal Adhesion Kinase Pathways. LID - 10.3390/polym10091043 [doi] LID - 1043 AB - 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 IC(50) values of 1.56, 1.80, 1.57, and 1.73 microg/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. FAU - Zheng, Lanhong AU - Zheng L AD - School of Pharmacy, Shanghai University of Medicine & Health Sciences, Shanghai 201318, China. zhenglanhong@126.com. AD - Key Laboratory of Sustainable Development of Polar Fishery, Ministry of Agriculture, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao 266071, China. zhenglanhong@126.com. FAU - Zhu, Xiangjie AU - Zhu X AUID- ORCID: 0000-0003-1871-6755 AD - 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. AD - Shanghai Ocean University, Shanghai 201306, China. zhuxiangjie1204@163.com. FAU - Yang, Kangli AU - Yang K AUID- ORCID: 0000-0003-1871-6755 AD - 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. FAU - Zhu, Meihong AU - Zhu M AD - 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. FAU - Farooqi, Ammad Ahmad AU - Farooqi AA AD - Institute of Biomedical and Genetic Engineering (IBGE), Islamabad 44000, Pakistan. ammadfarooqi@rlmclahore.com. FAU - Kang, Daole AU - Kang D AD - 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. FAU - Sun, Mi AU - Sun M AD - 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. FAU - Xu, Yixin AU - Xu Y AD - School of Pharmacy, Shanghai University of Medicine & Health Sciences, Shanghai 201318, China. xuyx@sumhs.edu.cn. FAU - Lin, Xiukun AU - Lin X AD - Department of Pharmacology, Southwest Medical University, Luzhou 646000, Sichuan, China. xiukunlin@126.com. FAU - Feng, Yingang AU - Feng Y AUID- ORCID: 0000-0002-0879-1316 AD - 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. FAU - Liang, Fangfang AU - Liang F AD - 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. FAU - Zhang, Fuming AU - Zhang F AD - 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. FAU - Linhardt, Robert J AU - Linhardt RJ AUID- ORCID: 0000-0003-2219-5833 AD - 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. LA - eng GR - 2014B01YQ01/Special Scientific Research Funds for Central Non-profit Institutes, Chinese Academy of Fishery Sciences/ GR - 2014GSF121016/the Science and Technology Development Plans of Shandong Province/ GR - 20603022013017/the Special Scientific Research Funds for Central Non-profit Institutes, Yellow Sea Fisheries Research Institutes/ GR - 20603022012013/the Special Scientific Research Funds for Central Non-profit Institutes, Yellow Sea Fisheries Research Institutes/ PT - Journal Article DEP - 20180919 PL - Switzerland TA - Polymers (Basel) JT - Polymers JID - 101545357 EIN - Polymers (Basel). 2021 Jan 05;13(1):. PMID: 33466568 PMC - PMC6403900 OTO - NOTNLM OT - FAK OT - cytotoxicity OT - invasion OT - polypeptide COIS- The authors declare no conflict of interest. EDAT- 2019/04/10 06:00 MHDA- 2019/04/10 06:01 PMCR- 2018/09/19 CRDT- 2019/04/10 06:00 PHST- 2018/03/12 00:00 [received] PHST- 2018/04/20 00:00 [revised] PHST- 2018/05/02 00:00 [accepted] PHST- 2019/04/10 06:00 [entrez] PHST- 2019/04/10 06:00 [pubmed] PHST- 2019/04/10 06:01 [medline] PHST- 2018/09/19 00:00 [pmc-release] AID - polym10091043 [pii] AID - polymers-10-01043 [pii] AID - 10.3390/polym10091043 [doi] PST - epublish SO - Polymers (Basel). 2018 Sep 19;10(9):1043. doi: 10.3390/polym10091043.