Dichloroacetic acid (DCA) synergizes with the SIRT2 inhibitor Sirtinol and AGK2 to enhance anti-tumor efficacy in non-small cell lung cancer
文献类型：期刊论文
| 作者 | Ma, Wenjing1,2,4; Wang, Kaiying1,2; Huang, Gang1,2,3,4; Zhao, Xiaoping3; Liu, Jianjun3; , |
| 刊名 | CANCER BIOLOGY & THERAPY
 |
| 出版日期 | 2018 |
| 卷号 | 19期号:9页码:835-846 |
| 关键词 | Sodium dichloroacetic acid (DCA) SIRT2 warburg effect PDHA1 drug synergy |
| ISSN号 | 1538-4047 |
| DOI | 10.1080/15384047.2018.1480281 |
| 文献子类 | Article |
| 英文摘要 | Combination chemotherapy is a potentially promising approach to enhance anticancer activity, overcome drug resistance, and improve disease-free and overall survival. The current study investigates the antitumor activity of sodium dichloroacetic acid (DCA) in combination with SIRT2 inhibitor Sirtinol and AGK2. We found that combining DCA with Sirtinol produced a synergistic therapeutic benefit in A549 and H1299 NSCLC cells in vitro and in a mouse A549 xenograft model. Synergistic potentiation of oxidative phosphorylation (OXPHOS) was observed, including decreased glucose consumption, decreased lactate production, increased OCR and increased ROS generation, possibly via co-targeting pyruvate dehydrogenase alpha 1(PDHA1). Mechanically, AGK2 and Sirtinol were found to increase the lysine-acetylation and decrease the serine-phosphorylation of PDHA1, which enabled the two inhibitors to synergize with DCA to further activate PDHA1. Besides, a AMPK-ROS feed-forward loop was notably activated after the combined treatments compared with mono-therapy. Our results indicate that the combination of DCA and SIRT2 inhibitor may provide a promising therapeutic strategy to effectively kill cancer cells. |
| 学科主题 | Oncology |
| WOS关键词 | PYRUVATE-DEHYDROGENASE COMPLEX ; NAD-DEPENDENT DEACETYLASES ; PHOSPHOGLYCERATE MUTASE ; HISTONE DEACETYLASE ; DRUG-COMBINATION ; OXIDATIVE STRESS ; TUMOR-GROWTH ; PHOSPHORYLATION ; DEATH ; AMPK |
| 语种 | 英语 |
| WOS记录号 | WOS:000445471200010 |
| 出版者 | TAYLOR & FRANCIS INC |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/850]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所 |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Hlth Sci, Key Lab Stem Cell Biol, Shanghai, Peoples R China; 2.Shanghai Jiao Tong Univ, Sch Med, Shanghai, Peoples R China; 3.Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Dept Nucl Med, Shanghai, Peoples R China; 4.Shanghai Univ Med & Hlth Sci, Shanghai Key Lab Mol Imaging, Shanghai 201318, Peoples R China, |
| 推荐引用方式 GB/T 7714 | Ma, Wenjing,Wang, Kaiying,Huang, Gang,et al. Dichloroacetic acid (DCA) synergizes with the SIRT2 inhibitor Sirtinol and AGK2 to enhance anti-tumor efficacy in non-small cell lung cancer[J]. CANCER BIOLOGY & THERAPY,2018,19(9):835-846. |
| APA | Ma, Wenjing,Wang, Kaiying,Huang, Gang,Zhao, Xiaoping,Liu, Jianjun,&,.(2018).Dichloroacetic acid (DCA) synergizes with the SIRT2 inhibitor Sirtinol and AGK2 to enhance anti-tumor efficacy in non-small cell lung cancer.CANCER BIOLOGY & THERAPY,19(9),835-846. |
| MLA | Ma, Wenjing,et al."Dichloroacetic acid (DCA) synergizes with the SIRT2 inhibitor Sirtinol and AGK2 to enhance anti-tumor efficacy in non-small cell lung cancer".CANCER BIOLOGY & THERAPY 19.9(2018):835-846. |
入库方式： OAI收割
来源：上海营养与健康研究所
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