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
- Files in This Item
There are no attached files.