Bifunctional autophagic flux by 2-deoxyglucse to control survival or growth of prostate cancer cells

Objectives Recent 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. In order to find out whether autophagy is harmful or helpful for PC3 cell survival and growth under nutrient-depleted conditions by 2DG, we investigated 2DG’s effect on autophagy regulation in PC3 cells

Methods Prostate cancer cells (PC3) were treated with 2DG for 6 hours or 48 hours to analyze the changing of cell cycle and autophagy flux. Rapamycin and LC3B overexpressing vector were administrated to PC3 cells for autophagy induction and chloroquine and shBeclin1 plasmid were used to inhibit autophagy in PC3 cells.

Results we demonstrated that 2DG inhibits prostate cancer cell (PC3) 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 hours, despite autophagy-inducing internal signaling being maintained. This relationship between cell growth and autophagy was confirmed. Increased autophagic flux by rapamycin or LC3B overexpression significantly reduced cell growth, while autophagy inhibition with shBeclin1 plasmid or chloroquine had no significant effect on regulating cell growth

Conclusions maintaining increased autophagic flux was more effective at inhibiting cancer cell progression than inhibition of autophagic flux, which could be 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 this regulation can be a suitable target for cancer therapy