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Deguelin inhibits non-small cell lung cancer via down-regulating Hexokinases II-mediated glycolysis

2017; Impact Journals LLC; Volume: 8; Issue: 20 Linguagem: Inglês

10.18632/oncotarget.15937

1949-2553

Wei Li, Gao Feng, Xiaoqian Ma, Ruike Wang, Xin Dong, Wei Wang,

Epigenetics and DNA Methylation

// Wei Li 1, 2, * , Feng Gao 3, 4, * , Xiaoqian Ma 1, 2, * , Ruike Wang 5, * , Xin Dong 6 , Wei Wang 1, 2 1 Department of Radiology, The Third Xiangya Hospital of Central South University, Changsha, Hunan, 410000, P.R. China 2 Cell Transplantation and Gene Therapy Institute, The 3rd Xiangya Hospital of Central South University, Changsha, Hunan, 410000, P.R. China 3 Powder Metallurgy Research Institute of Central South University, Changsha, Hunan, 41000, P.R. China 4 Department of Ultrasonography, The 3rd Xiangya Hospital of Central South University, Changsha, Hunan, 410000, P.R. China 5 Xiangya School of Medicine, Central South University, Changsha, Hunan, 410000, P.R.China 6 State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100000, P.R. China * These authors contributed equally to this work Correspondence to: Wei Wang, email: weiw_bio@163.com Keywords: non-small cell lung cancer, deguelin, Hexokinases II, Akt, glycolysis Received: October 10, 2016 Accepted: February 22, 2017 Published: March 06, 2017 ABSTRACT Hexokinases II (HK2) is a hub in the regulation of cancer cell glycolysis. Here we reported deguelin, a natural compound which has been studied in various tumor types, has a profound anti-tumor effect on human non-small cell lung cancer (NSCLC) via directly down-regulating of glycolysis. In NSCLC cell lines and primary NSCLC tissue, we found HK2 is overexpressed. Deguelin treatment markedly inhibited anchorage-dependent and independent growth of NSCLC cell lines. We revealed that deguelin exposure impaired glucose metabolism by inhibiting Akt-mediated Hexokinase II expression, overexpression of constitutively activated Akt1 substantially rescued deguelin-induced glycolysis suppression. Moreover, deguelin suppressed HK2 presence on mitochondrial outer membrane and induced apoptosis. The in vivo data indicated that deguelin prominently restrained tumor development in a xenograft mouse model. Thus, deguelin appears to be a promising new therapeutic agent for lung cancer and may be considered for further studies in other animal models and in clinical trials.