Carbohydrate-based inducers of cellular stress for targeting cancer cells

Abstract

Small molecules that block the altered metabolism in cancer or increase the production of reactive oxygen species (ROS) are emerging as potential anti-cancer agents. Considering that various carbohydrates can be used for cellular energetics or protein N-glycosylation of which interruption can lead to cellular stress, we have synthesized and evaluated a library of N-aryl glycosides for induction of ROS and cytotoxicity in H1299 cancer cell line. Two N-aryl glycosides (K8 and H8) were identified that induce about 2-fold induction of ROS and cytotoxicity in H1299 cells. We further showed that the acetylated form of K8 (K8A) activates AMPK, and stabilizes p53 in HEK293 cells, and induce a higher cytotoxicity than 2-deoxy-d-glucose in H1299 cell line.