5-Nitro-5'-hydroxy-indirubin-3'-oxime (AGM130), an indirubin-3'-oxime derivative, inhibits tumor growth by inducing apoptosis against non-small cell lung cancer in vitro and in vivo.

Abstract

This study examined the anti-tumor effects of AGM130, a novel indirubin-3'-oxime derivative in A549 human non-small cell lung cancer cells. AGM130 significantly inhibited the proliferation and arrested the cell cycle of G2/M phase. Induction of apoptosis was detected in AGM130-treated A549 cells. The protein levels of Cytochrome c release, Bax, cleaved caspases and PARP were increased in AGM130 treated cells, whereas Bcl-2 levels were decreased. AGM130 inhibited Insulin-like growth factor 1 receptor (IGF1R), AKT/mTOR signaling and inactivated mitogen-activated protein kinases (MAPK). AGM130 also induced slight autophagy as pro-survival function and autophagy inhibition by chloroquine (CQ) induced necrosis. In vivo tumor xenograft model, AGM130 dose-dependently suppressed transplanted A549 cell tumor growth and induced the expression of proliferative cell nuclear antigen (PCNA). AGM130 also increased TUNEL positive apoptotic cell populations and the induction of glandular differentiation with mucin pool compared with vehicle-treated control in tumor tissue. These results suggest that AGM130 is an effective novel indirubin-3'-oxime derivative of anti-cancer drug and may be an attractive candidate for non-small cell lung cancer therapy.

• Authors: Mee-Young Ahn, Tae-Hyung Kim, Seong-Min Kwon, Hyo-Eun Yoon, Hyung-Sik Kim, Jae-Il Kim, Yong-Chul Kim, Keon-Wook Kang, Sang-Gun Ahn, Jung-Hoon Yoon
• Journal: European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences (Eur J Pharm Sci) Vol. 79 Pg. 122-31 (Nov 15 2015) ISSN: 1879-0720 [Electronic] Netherlands
• PMID: 26342773 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• 5-nitro-5'-hydroxyindirubin-3'-oxime
• Antineoplastic Agents
• IGF1R protein, human
• Indoles
• Oximes
• Receptors, Somatomedin
• indirubin-3'-monoxime
• Receptor, IGF Type 1
• Oncogene Protein v-akt

Topics

• Animals
• Antineoplastic Agents (therapeutic use)
• Apoptosis
• Carcinoma, Non-Small-Cell Lung (drug therapy)
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Humans
• Indoles (pharmacology, therapeutic use)
• Lung Neoplasms (drug therapy)
• MAP Kinase Signaling System (drug effects)
• Male
• Mice
• Mice, Nude
• Neoplasm Transplantation
• Oncogene Protein v-akt (antagonists & inhibitors)
• Oximes (pharmacology, therapeutic use)
• Receptor, IGF Type 1
• Receptors, Somatomedin (antagonists & inhibitors)