Anti-tumor Activity of Novel Indirubin Derivatives in Rat Tumor Model
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lndil‘ ubin is the active ingredient of Danggui Longhui Wan‘ a mixture of herbal medici l1e t hat is used to treat chronic myelocytic leukemia in tradi t ional Chinese medicine‘ He re, we show that new indirubin deri vatives 5' -ni tro-indirubinoxime, 5' -f1 uoro-indiru binoxime and 5’ -tri rnethylacetamino-i nd i 1'1.1 bi noxi me‘ have potent a n ti- proliferative activity on various human cancer cells and oncogenic RK3E-ras rat kidney cells with lC50 con centration ranging from 1-25 μ M, When the RK3E-ras cells were treated with indirubin derivatives for 24 h, the activity of caspase-3 and caspasc-7 was induccd followed by apoptosis , 011 the other hand, the activity of SAPK/JNK was inhi bited over the same period , lndirubin deri vatives a lso s howed strong ant i-tumor activity in rat s이 id and oral tumor models The inhibition of tlUl10r g:rowth was observed in animals beaJ‘ing RK3E-ras-induced turnor given subcutaneous dose of 100 mg/kg every other day for 10 days, Histologically, μeatment of indirubin derivatives caused significant inhibition of tumor formation associated wi th increased apoptosis and decreased proliferation of tumor cell s , These findings provide the potential value of indirubin derivatives as a novel candi date fOl 없l tJ -cancer agents ,