L-arginine처리를 통한 암세포의 시스플라틴 반응성 개선 및 Argininosuccinate synthetase 발현정도와 연관된 단독작용 효과로서의 세포사멸유도

Abstract

The association is well known between cisplatin-resistance and the loss of endogenous argininosuccinate synthetase (ASS1) expression in various cancer cells. Except for the on-target effect of cisplatin resistance related with epigenetic silencing of ASS1, other resistance mechanisms in cancer cells is currently unclear. ASS1 is a key enzyme and rate-limiting step in arginine synthesis, there is a possibility of the signaling alteration triggered by different ASS1 expression level or by cellular arginine availability. In other words, there is potential to ameliorate the cisplatin sensitivity via alteration of intracellular signaling or metabolic change driven by ASS1 itself or arginine. Given this circumstance, we aim to investigate how the ASS1 expression level and arginine supply effect on cisplatin-resistance and survival in cancer cells in terms of cellular signaling. We found not only exogenous arginine supply restores cisplatin-sensitivity in cancer cells but also arginine supply alone could negatively associate with cancer cell survival by alteration of certain signaling molecules according to ASS1 expression level.