Archives of Pharmacal Research

, Volume 32, Issue 6, pp 915–922

Anti-tumor activity of noble indirubin derivatives in human solid tumor models In Vitro

  • Soo-Hyun Kim
  • Soo Jeong Choi
  • Yong-Chul Kim
  • Hyo-Jeong Kuh
Research Articles Drug Actions

DOI: 10.1007/s12272-009-1614-2

Cite this article as:
Kim, SH., Choi, S.J., Kim, YC. et al. Arch. Pharm. Res. (2009) 32: 915. doi:10.1007/s12272-009-1614-2

Abstract

Indirubin has been identified as a component of a traditional Chinese medicine, Danggui Longhui Wan, which is used for the treatment of chronic myelogenous leukemia. Indirubin inhibits cyclin-dependent kinases (CDKs) and induces cell cycle arrest and apoptosis in cancer cells. Many indirubin derivatives have been studied for their potential anti-solid tumor activity. We have synthesized and evaluated many indirubin derivatives. In order to compare and confirm the potential of our major derivatives as anti-solid tumor agents, we examined their anti-proliferative activity in monolayers, as well as in multicellular spheroids (MCS) cultures of human colorectal cancer cells, DLD-1 and HT-29. The MCS model is an in vitro solid tumor model that is increasingly used for the evaluation of anti-solid tumor activity. 5-nitro-indirubin-3′-oxime (4c) and 5′-bromo-5-nitro-indirubin-3′-oxime (4l), compared to 5-trimethylacetamido-indirubin-3′-oxime (11) and 5-diphenylacetamido-indirubin-3′-oxime (33) showed greater anti-proliferative effects in monolayers, but lower anti-proliferative effects in MCS. Overall, our data suggest that compounds 11 and 33 may exert a significant anti-solid tumor activity via a mechanism other than CDK inhibition, different from that of 4c and 4l. These compounds are worth further investigation with respect to their anti-solid tumor activity and their mechanism of action in various solid tumor models.

Key words

Indirubin derivatives Multicellular spheroids (MCS) Antitumor activity Colon cancer In vitro 

Copyright information

© The Pharmaceutical Society of Korea 2009

Authors and Affiliations

  • Soo-Hyun Kim
    • 1
  • Soo Jeong Choi
    • 2
  • Yong-Chul Kim
    • 2
  • Hyo-Jeong Kuh
    • 1
  1. 1.Department of Biomedical Sciences, College of MedicineThe Catholic University of KoreaSeoulKorea
  2. 2.Department of Life ScienceGwangju Institute of Science and TechnologyGwangjuKorea

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