3-bromopyruvate and buthionine sulfoximine effectively kill anoikis-resistant hepatocellular carcinoma cells.
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-bromopyr...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2017-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5376082?pdf=render |
| _version_ | 1818478363109490688 |
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| author | Minjong Lee Ara Jo Seulki Lee Jong Bin Kim Young Chang Joon Yeul Nam Hyeki Cho Young Youn Cho Eun Ju Cho Jeong-Hoon Lee Su Jong Yu Jung-Hwan Yoon Yoon Jun Kim |
| author_facet | Minjong Lee Ara Jo Seulki Lee Jong Bin Kim Young Chang Joon Yeul Nam Hyeki Cho Young Youn Cho Eun Ju Cho Jeong-Hoon Lee Su Jong Yu Jung-Hwan Yoon Yoon Jun Kim |
| author_sort | Minjong Lee |
| collection | DOAJ |
| description | 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.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.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.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. |
| first_indexed | 2024-12-10T09:47:08Z |
| format | Article |
| id | doaj.art-f3994647be0344ec9a630b79ed2433a0 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T09:47:08Z |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-f3994647be0344ec9a630b79ed2433a02022-12-22T01:53:47ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01123e017427110.1371/journal.pone.01742713-bromopyruvate and buthionine sulfoximine effectively kill anoikis-resistant hepatocellular carcinoma cells.Minjong LeeAra JoSeulki LeeJong Bin KimYoung ChangJoon Yeul NamHyeki ChoYoung Youn ChoEun Ju ChoJeong-Hoon LeeSu Jong YuJung-Hwan YoonYoon Jun KimAcquisition 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.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.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.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.http://europepmc.org/articles/PMC5376082?pdf=render |
| spellingShingle | Minjong Lee Ara Jo Seulki Lee Jong Bin Kim Young Chang Joon Yeul Nam Hyeki Cho Young Youn Cho Eun Ju Cho Jeong-Hoon Lee Su Jong Yu Jung-Hwan Yoon Yoon Jun Kim 3-bromopyruvate and buthionine sulfoximine effectively kill anoikis-resistant hepatocellular carcinoma cells. PLoS ONE |
| title | 3-bromopyruvate and buthionine sulfoximine effectively kill anoikis-resistant hepatocellular carcinoma cells. |
| title_full | 3-bromopyruvate and buthionine sulfoximine effectively kill anoikis-resistant hepatocellular carcinoma cells. |
| title_fullStr | 3-bromopyruvate and buthionine sulfoximine effectively kill anoikis-resistant hepatocellular carcinoma cells. |
| title_full_unstemmed | 3-bromopyruvate and buthionine sulfoximine effectively kill anoikis-resistant hepatocellular carcinoma cells. |
| title_short | 3-bromopyruvate and buthionine sulfoximine effectively kill anoikis-resistant hepatocellular carcinoma cells. |
| title_sort | 3 bromopyruvate and buthionine sulfoximine effectively kill anoikis resistant hepatocellular carcinoma cells |
| url | http://europepmc.org/articles/PMC5376082?pdf=render |
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