The Effect of HSF1 Activity Inhibitor of the Cardenolide Group (CL-43) on Tumor and Nontransformed Cells

The occurrence of intolerable side effects in patients undergoing chemotherapy continues to be a key clinical obstacle. In this regard, the search for tumor-specific therapy that does not have a toxic effect on healthy tissue remains an urgent task. It is known that heat-shock protein factor HSF1 is an important marker of cancer progression, and the products of its transcriptional activity allow tumor cells to successfully avoid the negative effects of antitumor therapy. Thereby, the use of drugs that inhibit HSF1 activity is a promising strategy. In this research, we found that the HSF1 activity inhibitor from the CL-43 cardenolide group exhibited a cytoprotective effect on primary nontransformed dermal fibroblast cells (DF-2) and made them less sensitive to etoposide, while in DLD1 tumor cells, on the contrary, we observed an increase in this sensitivity. In addition, we found that CL-43 affected the intranuclear transport of active HSF1, as well as increasing its activity and, accordingly, the synthesis of HSP70 in human fibroblasts, while CL-43 suppressed this activity in a dose-dependent manner in tumor cells. Our results indicate the high therapeutic potential of CL-43 and its uniqueness as a tumor-specific compound.