The bifunctional autophagic flux by 2-deoxyglucose to control survival or growth of prostate cancer cells

BMC Cancer

Research Article

Seung Won Kim¹  Mijin Yun²  Jeong Yong Jeon²  Ki Cheong Park³ 

[1]Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, 120-752, Seoul, South Korea

[2]Severance Biomedical Science Institute, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, 120-752, Seoul, South Korea

[3]Department of Nuclear Medicine, Severance Hospital, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, 120-752, Seoul, South Korea

[4]Department of Surgery, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, 120-752, Seoul, South Korea

关键词: Rapamycin;    Endoplasmic Reticulum Stress;    LNCaP Cell;    Autophagic Cell Death;    Autophagy Inhibition;   

DOI  :  10.1186/s12885-015-1640-z

 received in 2014-11-25, accepted in 2015-09-01,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundRecent reports using metabolism regulating drugs showed that nutrient deprivation was an efficient tool to suppress cancer progression. In addition, autophagy control is emerging to prevent cancer cell survival. Autophagy breaks down the unnecessary cytoplasmic components into anabolic units and energy sources, which are the most important sources for making the ATP that maintains homeostasis in cancer cell growth and survival. Therefore, the glucose analog 2-deoxyglucose (2DG) has been used as an anticancer reagent due to its inhibition of glycolysis.MethodsProstate cancer cells (PC3) were treated with 2DG for 6 h or 48 h to analyze the changing of cell cycle and autophagic flux. Rapamycin and LC3B overexpressing vectors were administered to PC3 cells for autophagy induction and chloroquine and shBeclin1 plasmid were used to inhibit autophagy in PC3 cells to analyze PC3 cells growth and survival. The samples for western blotting were prepared in each culture condition to confirm the expression level of autophagy related and regulating proteins.ResultsWe demonstrated that 2DG inhibits PC3 cells growth and had discriminating effects on autophagy regulation based on the different time period of 2DG treatment to control cell survival. Short-term treatment of 2DG induced autophagic flux, which increased microtubule associated protein 1 light chain 3B (LC3B) conversion rates and reduced p62 levels. However, 2DG induced autophagic flux is remarkably reduced over an extended time period of 2DG treatment for 48 h despite autophagy inducing internal signaling being maintained. The relationship between cell growth and autophagy was proved. Increased autophagic flux by rapamycin or LC3B overexpression powerfully reduced cell growth, while autophagy inhibition with shBeclin1 plasmid or chloroquine had no significant effect on regulating cell growth.ConclusionGiven these results, maintaining increased autophagic flux was more effective at inhibiting cancer cell progression than inhibition of autophagic flux, which is necessary for the survival of PC3 cells. Autophagic flux should be tightly regulated to maintain metabolic homeostasis for cancer cell growth and survival in PC3 cells and is a suitable target for cancer therapy.

【 授权许可】

CC BY   
© Jeon et al. 2015