Biomol Ther  
Discovery of an Indirubin Derivative as a Novel c-Met Kinase Inhibitor with in vitro Anti-Tumor Effects
Karyn Muzinga Ndolo1, Su Jin An1, Kyeong Ryang Park1, Hyo Jeong Lee1, Kyoung Bin Yoon1, Yong-Chul Kim2 and Sun-Young Han1,*
¹College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, Jinju 52828,
²School of Life Sciences, Gwangju Institute of Science & Technology, Gwangju 61186, Republic of Korea
E-mail: syhan@gnu.ac.kr
Tel: +82-55-772-2423, Fax: +82-55-772-2429
Received: May 20, 2018; Revised: June 20, 2018; Accepted: June 26, 2018; Published online: July 30, 2018.
© The Korean Society of Applied Pharmacology. All rights reserved.

Abstract
The c-Met protein is a receptor tyrosine kinase involved in cell growth, proliferation, survival, and angiogenesis of several human tumors. Overexpression of c-Met has been found in gastric cancers and correlated with a poor prognosis. Indirubin is the active component of Danggui Longhui Wan, which is a traditional Chinese antileukemic recipe. In the present study, we tested the anti-cancer effects of an indirubin derivative, LDD-1937, on human gastric cancer cells SNU-638. When we performed the in vitro kinase assay against the c-Met activity, LDD-1937 inhibited the activity of c-Met. This result was confirmed by immunoblot and immunofluorescence of phosphorylated c-Met. Immunoblot analysis showed that LDD-1937 decreased the expression of the Erk1/2, STAT3, STAT5, and Akt, downstream proteins of c-Met. In addition, LDD-1937 reduced the cell viability and suppressed colony formation and migration of SNU-638 cells. Furthermore, LDD-1937 induced G2/M phase arrest in the SNU-638 cells by decreasing the expression levels of cyclin B1 and CDC2. Cleaved-PARP, an apoptosis-related protein, was up-regulated in cells treated with LDD-1937. Overall, this study suggests that LDD-1937 may be a novel small-molecule with therapeutic potential for selectively inhibiting c-Met and c-Met downstream pathways in human gastric cancers overexpressing c-Met.
Keywords: Gastric cancer, Indirubin, c-Met, LDD-1937


This Article


Cited By Articles
  • CrossRef (0)

e-submission

Archives