title: Rational design of selenadiazole derivatives to antagonize hyperglycemia-induced drug resistance in cancer cells.
abstract: Hyperglycemia is an important factor for chemoresistance of hepatocellular carcinoma patients with diabetes to therapeutics. In the present study, a series of selenadiazole derivatives have been rationally designed, synthesized, and found be able to antagonize drug resistance in HepG2 cells to doxorubicin (DOX) under simulated diabetes conditions. Hyperglycemia could promote the cell proliferation through upregulation of ERK and AKT phosphorylation. However, the synthetic selenadiazole derivatives effectively potentiated the cellular uptake of DOX and enhanced the antiproliferative activity of DOX on HepG2 cells by induction of apoptosis, via regulation of ROS-mediated AMPK activation, inhibition of mTORC1, and an increase in DNA damage. The selenadiazole derivatives that possess an increased lipophilicity could enhance the cellular uptake and anticancer efficacy of DOX. Taken together, this study provides a rational design strategy of selenadiazole derivatives to overcome hyperglycemia-induced drug resistance.
authors: Department of Chemistry, Jinan University, Guangzhou 510631 (P. R. China).
authors: Yuedan
authors: Y
authors: Liu
authors: Yi
authors: Y
authors: Luo
authors: Xiaoling
authors: X
authors: Li
authors: Wenjie
authors: W
authors: Zheng
authors: Tianfeng
authors: T
authors: Chen
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D006801:Humans; D015394:Molecular Structure; D018036:Selenium Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents; D018036:Selenium Compounds; D004317:Doxorubicin
keywords: apoptosis; cancer; chemoresistance; hyperglycemia; medicinal chemistry; organoselenium