PBN11-8, a Cytotoxic Polypeptide Purified from Marine Bacillus, Suppresses Invasion and Migration of Human Hepatocellular Carcinoma Cells by Targeting Focal Adhesion Kinase Pathways
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 cyto...
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ftdoajarticles:oai:doaj.org/article:41d705fce00443e89b92c95f463b8755 2023-05-15T13:46:44+02:00 PBN11-8, a Cytotoxic Polypeptide Purified from Marine Bacillus, Suppresses Invasion and Migration of Human Hepatocellular Carcinoma Cells by Targeting Focal Adhesion Kinase Pathways Lanhong Zheng Xiangjie Zhu Kangli Yang Meihong Zhu Ammad Ahmad Farooqi Daole Kang Mi Sun Yixin Xu Xiukun Lin Yingang Feng Fangfang Liang Fuming Zhang Robert J. Linhardt 2018-09-01T00:00:00Z https://doi.org/10.3390/polym10091043 https://doaj.org/article/41d705fce00443e89b92c95f463b8755 EN eng MDPI AG http://www.mdpi.com/2073-4360/10/9/1043 https://doaj.org/toc/2073-4360 2073-4360 doi:10.3390/polym10091043 https://doaj.org/article/41d705fce00443e89b92c95f463b8755 Polymers, Vol 10, Iss 9, p 1043 (2018) polypeptide cytotoxicity FAK invasion Organic chemistry QD241-441 article 2018 ftdoajarticles https://doi.org/10.3390/polym10091043 2022-12-31T01:54:36Z 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. Article in Journal/Newspaper Antarc* Antarctic Directory of Open Access Journals: DOAJ Articles Antarctic The Antarctic Polymers 10 9 1043 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
polypeptide cytotoxicity FAK invasion Organic chemistry QD241-441 |
spellingShingle |
polypeptide cytotoxicity FAK invasion Organic chemistry QD241-441 Lanhong Zheng Xiangjie Zhu Kangli Yang Meihong Zhu Ammad Ahmad Farooqi Daole Kang Mi Sun Yixin Xu Xiukun Lin Yingang Feng Fangfang Liang Fuming Zhang Robert J. Linhardt PBN11-8, a Cytotoxic Polypeptide Purified from Marine Bacillus, Suppresses Invasion and Migration of Human Hepatocellular Carcinoma Cells by Targeting Focal Adhesion Kinase Pathways |
topic_facet |
polypeptide cytotoxicity FAK invasion Organic chemistry QD241-441 |
description |
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. |
format |
Article in Journal/Newspaper |
author |
Lanhong Zheng Xiangjie Zhu Kangli Yang Meihong Zhu Ammad Ahmad Farooqi Daole Kang Mi Sun Yixin Xu Xiukun Lin Yingang Feng Fangfang Liang Fuming Zhang Robert J. Linhardt |
author_facet |
Lanhong Zheng Xiangjie Zhu Kangli Yang Meihong Zhu Ammad Ahmad Farooqi Daole Kang Mi Sun Yixin Xu Xiukun Lin Yingang Feng Fangfang Liang Fuming Zhang Robert J. Linhardt |
author_sort |
Lanhong Zheng |
title |
PBN11-8, a Cytotoxic Polypeptide Purified from Marine Bacillus, Suppresses Invasion and Migration of Human Hepatocellular Carcinoma Cells by Targeting Focal Adhesion Kinase Pathways |
title_short |
PBN11-8, a Cytotoxic Polypeptide Purified from Marine Bacillus, Suppresses Invasion and Migration of Human Hepatocellular Carcinoma Cells by Targeting Focal Adhesion Kinase Pathways |
title_full |
PBN11-8, a Cytotoxic Polypeptide Purified from Marine Bacillus, Suppresses Invasion and Migration of Human Hepatocellular Carcinoma Cells by Targeting Focal Adhesion Kinase Pathways |
title_fullStr |
PBN11-8, a Cytotoxic Polypeptide Purified from Marine Bacillus, Suppresses Invasion and Migration of Human Hepatocellular Carcinoma Cells by Targeting Focal Adhesion Kinase Pathways |
title_full_unstemmed |
PBN11-8, a Cytotoxic Polypeptide Purified from Marine Bacillus, Suppresses Invasion and Migration of Human Hepatocellular Carcinoma Cells by Targeting Focal Adhesion Kinase Pathways |
title_sort |
pbn11-8, a cytotoxic polypeptide purified from marine bacillus, suppresses invasion and migration of human hepatocellular carcinoma cells by targeting focal adhesion kinase pathways |
publisher |
MDPI AG |
publishDate |
2018 |
url |
https://doi.org/10.3390/polym10091043 https://doaj.org/article/41d705fce00443e89b92c95f463b8755 |
geographic |
Antarctic The Antarctic |
geographic_facet |
Antarctic The Antarctic |
genre |
Antarc* Antarctic |
genre_facet |
Antarc* Antarctic |
op_source |
Polymers, Vol 10, Iss 9, p 1043 (2018) |
op_relation |
http://www.mdpi.com/2073-4360/10/9/1043 https://doaj.org/toc/2073-4360 2073-4360 doi:10.3390/polym10091043 https://doaj.org/article/41d705fce00443e89b92c95f463b8755 |
op_doi |
https://doi.org/10.3390/polym10091043 |
container_title |
Polymers |
container_volume |
10 |
container_issue |
9 |
container_start_page |
1043 |
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1766245167415689216 |