- Guthrie, Margaret L;
- Sidhu, Preetpal S;
- Hill, Emily K;
- Horan, Timothy C;
- Nandhikonda, Premchendar;
- Teske, Kelly A;
- Yuan, Nina Y;
- Sidorko, Marina;
- Rodali, Revathi;
- Cook, James M;
- Han, Lanlan;
- Silvaggi, Nicholas R;
- Bikle, Daniel D;
- Moore, Richard G;
- Singh, Rakesh K;
- Arnold, Leggy A
Aim
To investigate the in vivo effects of 3-indolylmethanamines 31B and PS121912 in treating ovarian cancer and leukemia, respectively.Materials and methods
Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) and western blotting were applied to demonstrate the induction of apoptosis. Xenografted mice were investigated to show the antitumor effects of 3-indolylmethanamines. (13)C-Nuclear magnetic resource (NMR) and western blotting were used to demonstrate inhibition of glucose metabolism.Results
31B inhibited ovarian cancer cell proliferation and activated caspase-3, cleaved poly (ADP-ribose) polymerase 1 (PARP1), and phosphorylated mitogen-activated protein kinases (MAPK), JUN N-terminal kinase/stress-activated protein kinase (JNK/SAPK) and p38. 31B reduced ovarian cancer xenograft tumor growth and PS121912 inhibited the growth of HL-60-derived xenografts without any sign of toxicity. Compound 31B inhibited de novo glycolysis and lipogenesis mediated by the reduction of fatty acid synthase and lactate dehydrogenase-A expression.Conclusion
3-Indolylmethanamines represent a new class of antitumor agents. We have shown for the first time the in vivo anticancer effects of 3-indolylmethanamines 31B and PS121912.