CS-2765

Apoptosis

NKP-1339 (0-200 μM; 72 hours) has the anticancer activity against malignant cell lines of diverse origin, exhibits IC ₅₀ values of 45-200 μM for KP1339 mono-therapy. It against Hepatoma cell line, Hep3B, HepG2, PLC/PRF/5 and HCC2 cells with the Mean IC ₅₀ value of 186.3 μM, 165.4 μM, 124.4 μM, and 69.4 μM, respectively. It against Melanoma cell line, VM-1, VM-21,VM-48 with IC ₅₀ values of 178 μM, 111 μM, and 143 μM, respectively. It against Lung cancer and Colon cancer cell lines, inhibits A549, VL-8, SW480 and HCT116 cells, respectively. NKP-1339 (0-150 μM; 24 hours) induces cell apoptosis alone. When it combines with sorafenib, it increases the numbers of the apopotic cells. Additionally, the p-PARP and caspase 7 cleavage is promoted either. NKP-1339 (0-150 μM; 24 hours) can promote phosphorylation of STAT3 and CREB expression, however, the decreasation is inhibited by sorafenib cotreatment.

NKP-1339 (intravenous injection; 30 mg/kg; once a week; 42sdays) combines with the multi-kinase inhibitor sorafenib and exhibits a further anticancer activity when compares to the NKP-1339 treatment alone in Hep3B xenografts grown in Balb/c SCID mice .