Discovery and optimization of cardenolides inhibiting HSF1 activation in human colon HCT-116 cancer cells.

ABSTRACT: Combinational anticancer therapy demonstrates increased efficiency, as it targets different cell-survival mechanisms and allows the decrease of drug dosages that are often toxic to normal cells. Inhibitors of the heat shock response (HSR) are known to reduce the efficiency of proteostasis mechanisms in many cancerous cells, and therefore, may be employed as anti-tumor drug complements. However, the application of HSR inhibitors is limited by their cytotoxicity, and we suggested that milder inhibitors may be employed to sensitize cancer cells to a certain drug. We used a heat-shock element-luciferase reporter system and discovered a compound, CL-43, that inhibited the levels of heat shock proteins 40, 70 (Hsp70), and 90 kDa in HCT-116 cells and was not toxic for cells of several lines, incl

SUBMITTER: Nikotina AD 

PROVIDER: S-EPMC6007471 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature