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...
Published in: | Polymers |
---|---|
Main Authors: | , , , , , , , , , , , , |
Format: | Text |
Language: | English |
Published: |
Multidisciplinary Digital Publishing Institute
2018
|
Subjects: | |
Online Access: | https://doi.org/10.3390/polym10091043 |
id |
ftmdpi:oai:mdpi.com:/2073-4360/10/9/1043/ |
---|---|
record_format |
openpolar |
spelling |
ftmdpi:oai:mdpi.com:/2073-4360/10/9/1043/ 2023-08-20T04:01:31+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 Farooqi Daole Kang Mi Sun Yixin Xu Xiukun Lin Yingang Feng Fangfang Liang Fuming Zhang Robert Linhardt 2018-09-19 application/pdf https://doi.org/10.3390/polym10091043 EN eng Multidisciplinary Digital Publishing Institute https://dx.doi.org/10.3390/polym10091043 https://creativecommons.org/licenses/by/4.0/ Polymers; Volume 10; Issue 9; Pages: 1043 polypeptide cytotoxicity FAK invasion Text 2018 ftmdpi https://doi.org/10.3390/polym10091043 2023-07-31T21:44:19Z 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. Text Antarc* Antarctic MDPI Open Access Publishing Antarctic The Antarctic Polymers 10 9 1043 |
institution |
Open Polar |
collection |
MDPI Open Access Publishing |
op_collection_id |
ftmdpi |
language |
English |
topic |
polypeptide cytotoxicity FAK invasion |
spellingShingle |
polypeptide cytotoxicity FAK invasion Lanhong Zheng Xiangjie Zhu Kangli Yang Meihong Zhu Ammad Farooqi Daole Kang Mi Sun Yixin Xu Xiukun Lin Yingang Feng Fangfang Liang Fuming Zhang Robert 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 |
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 |
Text |
author |
Lanhong Zheng Xiangjie Zhu Kangli Yang Meihong Zhu Ammad Farooqi Daole Kang Mi Sun Yixin Xu Xiukun Lin Yingang Feng Fangfang Liang Fuming Zhang Robert Linhardt |
author_facet |
Lanhong Zheng Xiangjie Zhu Kangli Yang Meihong Zhu Ammad Farooqi Daole Kang Mi Sun Yixin Xu Xiukun Lin Yingang Feng Fangfang Liang Fuming Zhang Robert 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 |
Multidisciplinary Digital Publishing Institute |
publishDate |
2018 |
url |
https://doi.org/10.3390/polym10091043 |
geographic |
Antarctic The Antarctic |
geographic_facet |
Antarctic The Antarctic |
genre |
Antarc* Antarctic |
genre_facet |
Antarc* Antarctic |
op_source |
Polymers; Volume 10; Issue 9; Pages: 1043 |
op_relation |
https://dx.doi.org/10.3390/polym10091043 |
op_rights |
https://creativecommons.org/licenses/by/4.0/ |
op_doi |
https://doi.org/10.3390/polym10091043 |
container_title |
Polymers |
container_volume |
10 |
container_issue |
9 |
container_start_page |
1043 |
_version_ |
1774724774038077440 |