Antitumor Activity of 3-Indolylmethanamines 31B and PS121912.

Abstract

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.

• Authors: Margaret L Guthrie, Preetpal S Sidhu, Emily K Hill, Timothy C Horan, Premchendar Nandhikonda, Kelly A Teske, Nina Y Yuan, Marina Sidorko, Revathi Rodali, James M Cook, Lanlan Han, Nicholas R Silvaggi, Daniel D Bikle, Richard G Moore, Rakesh K Singh, Leggy A Arnold
• Journal: Anticancer research (Anticancer Res) Vol. 35 Issue 11 Pg. 6001-7 (Nov 2015) ISSN: 1791-7530 [Electronic] Greece
• PMID: 26504023 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Chemical References

• 4-chloro-N-((2-chlorophenyl)(2-methyl-1H-indol-3-yl)methyl)aniline
• Amines
• Aniline Compounds
• Antineoplastic Agents
• Hydrocarbons, Aromatic
• Indoles
• PS121912

Topics

• Amines (chemistry)
• Aniline Compounds (pharmacology)
• Animals
• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Blotting, Western
• Cell Proliferation (drug effects)
• Female
• Flow Cytometry
• Humans
• Hydrocarbons, Aromatic (pharmacology)
• Indoles (chemistry, pharmacology)
• Magnetic Resonance Spectroscopy
• Mice
• Mice, Nude
• Ovarian Neoplasms (drug therapy, metabolism, pathology)
• Tumor Cells, Cultured
• Xenograft Model Antitumor Assays