Figure 2.

Combination of Tenovin-1 and metformin led to increased cell death in prostate cancer cells in a p53 dependent manner (A, B) Combination of Tenovin-1 and metformin induced an increased cell death in LNCaP and C4-2 cells. Cells as indicated were treated with either metformin or Tenovin-1 alone or together for 24 hours, and harvested for IB. (C, D) Metformin plus Tenovin-1 did not induce an increase of cell death in p53-negative prostate cancer cells. PC-3 (p53-null) and DU145 (p53 mutant) cells were treated with indicated drugs for 24 hours and harvested. (D, E) No increased cell death with metformin plus Tenovin-1 in LNCaP and C4-2 cells upon p53 depletion. Cells were depleted of p53 with lentivirus-based shRNA, treated with indicated drugs for 24 hours, and harvested. (F) Combination of Tenovin-1 and metformin led to significantly decreased colony formation. LNCaP cells were seeded in 6-well plates and treated with indicated drug(s) for 1 month, with medium changing and drug treatment every 3 days. Cells were fixed with formalin and stained with crystal violet. (G to J) Tenovin-1 treatment antagonized metformin-induced increased glycolysis. After LNCaP (G, H) and C4-2 (I, J) cells were cultured in 6-well plates and treated with indicated drug(s) for 24 hours, medium were harvested for glucose and lactate measurement. Relative glucose consumption rate and lactate production rate were calculated.