3-bromopyruvate and buthionine sulfoximine effectively killanoikis-resistant hepatocellular carcinoma cells

Collection with item attached
2017
Item details URL
http://open-repository.kisti.re.kr/cube/handle/open_repository/473423.do
DOI
10.1371/journal.pone.0174271
Title
3-bromopyruvate and buthionine sulfoximine effectively killanoikis-resistant hepatocellular carcinoma cells
Description
This study was supported by a grant from the Seoul National UniversityHospital Research Fund (0320150210 [2015-1108]), a grant (800-20140567)from the Ildong Pharmaceutical Co., Ltd. (Seoul, South Korea), and agrant of the Korea Health Technology R&D Project through the KoreaHealth Industry Development Institute (KHIDI), funded by the Ministry ofHealth & Welfare, Republic of Korea (H116C1074).
abstract
Background & aims
Acquisition of anoikis resistance is a prerequisite for metastasis in hepatocellular carcinoma (HCC). However, little is known about how energy metabolism and antioxidant systems are altered in anoikis-resistant (AR) HCC cells. We evaluated anti-tumor effects of a combination treatment of 3-bromopyruvate (3-BP) and buthionine sulfoximine (BSO) in AR HCC cells.
Methods
We compared glycolysis, reactive oxygen species (ROS) production, and chemoresistance among Huh-BAT, HepG2 HCC cells, and the corresponding AR cells. Expression of hexokinase II, gamma-glutamylcysteine synthetase (rGCS), and epithelial mesenchymal transition (EMT) markers in AR cells was assessed. Anti-tumor effects of a combination treatment of 3-BP and BSO were evaluated in AR cells and an HCC xenograft mouse model.
Results
AR HCC cells showed significantly higher chemoresistance, glycolysis and lower ROS production than attached cells. Expression of hexokinase II, rGCS, and EMT markers was higher in AR HCC cells than attached cells. A combination treatment of 3-BP/BSO effectively suppressed proliferation of AR HCC cells through apoptosis by blocking glycolysis and enhancing ROS levels. In xenograft mouse models, tumor growth derived from AR HCC cells was significantly suppressed in the group treated with 3-BP/BSO compared to the group treated with 3-BP or sorafenib.
Conclusions
These results demonstrated that a combination treatment of 3-BP/BSO had a synergistic anti-tumor effect in an AR HCC model. This strategy may be an effective adjuvant therapy for patients with sorafenib-resistant HCC.
provenance
Made available in Cube on 2018-09-28T10:19:08Z (GMT). No. of bitstreams: 0
language
English
author
Lee, Minjong
Jo, Ara
Lee, Seulki
Bin Kim, Jong
Chang, Young
Nam, Joon Yeul
Cho, Hyeki
Cho, Young Youn
Cho, Eun Ju
Lee, Jeong-Hoon
Yu, Su Jong
Yoon, Jung-Hwan
Kim, Yoon Jun
orcid
Yoon, Jung-Hwan/0000-0002-9128-3610; Cho, Hyeki/0000-0003-3694-8111; ,
minjong/0000-0002-3159-5444
accessioned
2018-09-28T10:19:08Z
available
2018-09-28T10:19:08Z
issued
2017
citation
PLOS ONE(12): 3
issn
1932-6203
uri
http://open-repository.kisti.re.kr/cube/handle/open_repository/473423.do
Funder
보건복지부
Funding Program
감염병위기대응기술개발
Project ID
1465022871
Jurisdiction
Rep.of Korea
Project Name
Genome-wide association study according to the treatment response in chronic hepatitis B patients and the pre-clinical study for novel hepatitis B viral therapeutics of multi-step viral life cycle inhibition combined with immune-modulation
rights
openAccess
type
article


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