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Cell death & disease
01 24, 2018;9 (2): 89.

Elimination of stem-like cancer cell side-population by auranofin through modulation of ROS and glycolysis.

Guo-Xin Hou, Pan-Pan Liu, Shengyi Zhang, Mengqi Yang, Jianwei Liao, Jing Yang, Yumin Hu, Wen-Qi Jiang, Shijun Wen, Peng Huang
Author Information
  1. Guo-Xin Hou: Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, China.
  2. Pan-Pan Liu: Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, China.
  3. Shengyi Zhang: Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, China.
  4. Mengqi Yang: Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, China.
  5. Jianwei Liao: Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, China.
  6. Jing Yang: Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, China.
  7. Yumin Hu: Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, China.
  8. Wen-Qi Jiang: Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, China.
  9. Shijun Wen: Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, China. wenshj@sysucc.org.cn.
  10. Peng Huang: Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, China. phuang@mdanderson.org.
PMID: 29367724 DOI: 10.1038/s41419-017-0159-4

Abstract

Cancer side-population (SP) represents a sub-population of stem-like cancer cells that have an important role in drug resistance due to their high expression of the ATP-binding cassette transporter ABCG2 involved in drug export. Auranofin (AF), a clinical drug of gold complex that is used in treatment of rheumatoid arthritis, has been reported inducing tumor antiproliferation. However, whether AF can impact SP cells remains unclear. Our study showed that AF caused a depletion of SP cells and a downregulation of stem cell markers, and impaired their ability to form tumor colonies in vitro and incidence to develop tumors in vivo of lung cancer cells. Reactive oxygen species (ROS) had an important role in mediating AF-induced depletion of SP cells, which could be reversed by antioxidant NAC. Further study revealed that AF could also cause ATP depletion by inhibition of glycolysis. The depletion of cellular ATP might impair the function of ABCG2 pump, leading to increased drug accumulation within the cells and thus enhancing anticancer activity of chemotherapeutic agents such as adriamycin. Synergistic effect of AF and adriamycin was demonstrated both in vitro and in vivo. Simultaneous increase of ROS and inhibition of glycolysis is a novel strategy to eliminate stem-like cancer cells. Combination of AF with adriamycin seems to be promising to enhance therapeutic effectiveness.

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MeSH Term

Adenosine Triphosphate
Animals
Auranofin
Biomarkers, Tumor
Carcinogenesis
Cell Line, Tumor
Deoxyglucose
Doxorubicin
Drug Synergism
Glycolysis
Hexokinase
Humans
Mice
Neoplastic Stem Cells
Reactive Oxygen Species
Side-Population Cells
Spheroids, Cellular
Xenograft Model Antitumor Assays

Chemicals

Biomarkers, Tumor
Reactive Oxygen Species
Auranofin
Doxorubicin
Adenosine Triphosphate
Deoxyglucose
Hexokinase
Journal Article Research Support, Non-U.S. Gov't
Article has an altmetric score of 1

Word Cloud

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