Resveratrol inhibits Hexokinases II mediated glycolysis in non-small cell lung cancer via targeting Akt signaling pathway.
Deregulation of glycolysis was often observed in human cancer cells. In the present study, we reported resveratrol, a small polyphenol, which has been intensively studied in various tumor models, has a profound anti-tumor effect on human non-small cell lung cancer (NSCLC) via regulation of glycolysis. Resveratrol impaired hexokinase II (HK2)-mediated glycolysis, and markedly inhibited anchorage-dependent and -independent growth of NSCLC cells. Exposure to resveratrol decreased EGFR and downstream kinases Akt and ERK1/2 activation. Moreover, we revealed that resveratrol impaired glucose metabolism by mainly inhibiting expression of HK2 mediated by the Akt signaling pathway, and exogenous overexpression of constitutively activated Akt1 in NSCLC cells substantially rescued resveratrol-induced glycolysis suppression. The in vivo data indicated that resveratrol obviously suppressed tumor growth in a xenograft mouse model. Our results suggest targeting HK2 or metabolic enzymes appears to be a new approach for clinical NSCLC prevention or treatment.
Department of Radiology, the 3rd Xiangya Hospital of Central South University, Changsha, Hunan 410000, PR China; Cell Transplantation and Gene Therapy Institute, the 3rd Xiangya Hospital of Central South University, Changsha, Hunan 410000, PR China.
Wei
W
Li
Department of Radiology, the 3rd Xiangya Hospital of Central South University, Changsha, Hunan 410000, PR China; Cell Transplantation and Gene Therapy Institute, the 3rd Xiangya Hospital of Central South University, Changsha, Hunan 410000, PR China.
Xiaoqian
X
Ma
Department of Radiology, the 3rd Xiangya Hospital of Central South University, Changsha, Hunan 410000, PR China; Cell Transplantation and Gene Therapy Institute, the 3rd Xiangya Hospital of Central South University, Changsha, Hunan 410000, PR China.
Na
N
Li
Department of Radiology, the 3rd Xiangya Hospital of Central South University, Changsha, Hunan 410000, PR China; Cell Transplantation and Gene Therapy Institute, the 3rd Xiangya Hospital of Central South University, Changsha, Hunan 410000, PR China.
Huasheng
H
Liu
Department of Radiology, the 3rd Xiangya Hospital of Central South University, Changsha, Hunan 410000, PR China; Cell Transplantation and Gene Therapy Institute, the 3rd Xiangya Hospital of Central South University, Changsha, Hunan 410000, PR China.
Qiong
Q
Dong
Department of Radiology, the 3rd Xiangya Hospital of Central South University, Changsha, Hunan 410000, PR China; Cell Transplantation and Gene Therapy Institute, the 3rd Xiangya Hospital of Central South University, Changsha, Hunan 410000, PR China.
Juan
J
Zhang
Department of Radiology, the 3rd Xiangya Hospital of Central South University, Changsha, Hunan 410000, PR China; Cell Transplantation and Gene Therapy Institute, the 3rd Xiangya Hospital of Central South University, Changsha, Hunan 410000, PR China.
Cejun
C
Yang
Department of Radiology, the 3rd Xiangya Hospital of Central South University, Changsha, Hunan 410000, PR China; Cell Transplantation and Gene Therapy Institute, the 3rd Xiangya Hospital of Central South University, Changsha, Hunan 410000, PR China.
Yin
Y
Liu
Department of Radiology, the 3rd Xiangya Hospital of Central South University, Changsha, Hunan 410000, PR China; Cell Transplantation and Gene Therapy Institute, the 3rd Xiangya Hospital of Central South University, Changsha, Hunan 410000, PR China.
Qi
Q
Liang
Department of Radiology, the 3rd Xiangya Hospital of Central South University, Changsha, Hunan 410000, PR China; Cell Transplantation and Gene Therapy Institute, the 3rd Xiangya Hospital of Central South University, Changsha, Hunan 410000, PR China.
Shengwang
S
Zhang
Department of Radiology, the 3rd Xiangya Hospital of Central South University, Changsha, Hunan 410000, PR China; Cell Transplantation and Gene Therapy Institute, the 3rd Xiangya Hospital of Central South University, Changsha, Hunan 410000, PR China.
Chang
C
Xu
Department of Urology, the First Affiliated Hospital of Hunan Normal University, People's Hospital of Hunan Province, Changsha, Hunan 410000, PR China.
Wei
W
Song
Department of Hematology, the 3rd Xiangya Hospital of Central South University, Changsha, Hunan 410000, PR China.
Shiming
S
Tan
Department of Radiology, the 3rd Xiangya Hospital of Central South University, Changsha, Hunan 410000, PR China; Cell Transplantation and Gene Therapy Institute, the 3rd Xiangya Hospital of Central South University, Changsha, Hunan 410000, PR China.
Pengfei
P
Rong
Department of Radiology, the 3rd Xiangya Hospital of Central South University, Changsha, Hunan 410000, PR China; Cell Transplantation and Gene Therapy Institute, the 3rd Xiangya Hospital of Central South University, Changsha, Hunan 410000, PR China. Electronic address: weiw_bio@163.com.
Wei
W
Wang
D017209:Apoptosis / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D006019:Glycolysis / Q000187:drug effects; D006593:Hexokinase / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects*; D013267:Stilbenes / Q000494:pharmacology*
D013267:Stilbenes; C000609700:HK2 protein, human; D006593:Hexokinase; D051057:Proto-Oncogene Proteins c-akt; D000077185:Resveratrol
Akt; Glycolysis; Hexokinases II; Non-small cell lung cancer; Resveratrol