흰쥐 종양 모델을 이용한 새로운 인디루빈 유도체의 종양 억제효과
윤정훈1, 권성민1, 김수아2, 안상건1
1조선대학교 치과대학 병리학교실, 2연세대학교 치과대학 병리학교실 및 구강종양연구소
Indirubin is the active ingredient of a traditional Chinese herbal medicine, Danggui Longhui Wan, used for the treatment of chronic myelocytic leukemia. Here, we report that novel indirubin derivatives, 5'-nitro-indirubinoxime (5'-NIO), 5'-fluoro-indirubinoxime (5'-FIO) and 5'-trimethylacetamino-indirubinoxime (5'-TAIO), have potent anti-proliferative activity on various human cancer cells and oncogenic RK3E-ras rat kidney cells with half-inhibitory concentrations (IC50) ranging from 1-12 M. Treatment with indirubin derivatives induced the activation of caspase 7 followed by apoptosis in RK3E-ras cells. Indirubin derivatives showed strong anti-tumor activity in rat solid and oral tumor models. Direct injection of indirubin derivatives every other day for 10 days induced significant inhibition of tumor growth in Sprague-Dawley rats bearing RK3E-ras-induced tumors. Histologically, treatment with indirubin derivatives caused significant inhibition of tumor formation with increased apoptosis and decreased tumor cell proliferation. These findings provide the potential value of indirubin derivatives as a novel candidate for anti-tumor agents.
*This work was supported by the Regional Technology Innovation Program of the Ministry of Commerce, Industry and Energy (MOCIE, Grant RT104-03-03), the 21C Frontier Microbial Genomic and Applications Center Program, Ministry of Science & Technology (Grant MG05-0304-3-0) and the Korea Research Foundation Grant funded by the Korean Government (MOEHRD, Basic Research Promotion Fund, KRF-2005-005-J05903).