Table 3.

Inhibition of Akt1 and Akt2 synergizes with multiple therapeutics in inducing caspase 3 activity

Cell lineCotreatmentFold caspase induction by Akti-1/2 over cotreatment alone
BT474Herceptin2.5
BT474γ-IR (8 Gy)22
MDA-MBA468Camptothecin2.4
HT29γ-IR (20 Gy)9
HT29Camptothecin7.7
A2780Purvalanol5.2
A2780Doxorubicin6.9
  • NOTE: Maximal induction of caspase-3 in combination drug treatments requires inhibition of Akt1 and Akt2. The ovarian A2780 and MDA-MB468 cell lines contain all three isoforms of Akt. The breast BT474 and colon HT29 cell lines contain only Akt1 and Akt2. The concentration of cotreatment was selected to give ∼2-fold increase in caspase-3 activity over untreated cells: doxorubicin, 2 μmol/L; camptothecin, 0.1 μmol/L, herceptin, 2 μmol/L; purvalanol, 2 μmol/L; Akti-1, 12 μmol/L; Akti-1/2, 5 μmol/L. LY294002 (20 μmol/L), an inhibitor of PI-3-K, blocks the activation of all Akt isoforms.