Abstract
1904
6-(1-Proproxyiminomethyl)-5,8-dimethoxy-1,4-naphthoquinone S-53 (DMNQ S-53) was synthesized to develop a novel anti-tumor agent against lung cancer. DMNQ S-53 exerted cytotoxicity against LLC cells with IC50 of ∼5_M. DMNQ S-53 also increased the sub G1 cell population stained by propidium iodide (PI) as well as ladder-like DNA fragmentation in a concentration dependent manner. Western blot analysis revealed that DMNQ S-53 induced apoptosis was associated with the activation of caspase-9 and -3, cleavage of poly (ADP-ribose) polymerase (PARP) and the increased ratio of Bax to Bcl-2 expression in LLC cells in a concentration dependent manner. In addition, DMNQ S-53 reduced mitochondrial potential suggesting the involvement of the mitochondrial intrinsic pathway. Furthermore, intraperitoneally injection of DMNQ S-53 resulted in the inhibition of the tumor volume/weight of LLC cells inoculated on the flank of C57BL6 mice up to ∼50%. Taken together, these results strongly indicate that DMNQ S-53 may inhibit LLC tumor growth in vitro and in vivo via apoptosis induction through the mitochondria-mediated caspase activation pathway.
98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA