Cardenolide-induced lysosomal membrane permeabilization demonstrates therapeutic benefits in experimental human non-small cell lung cancers

摘要: Non-small cell lung cancers (NSCLCs) are the leading cause of cancer deaths in most developed countries. Targeting heat shock protein 70 (Hsp70) expression and function, together with induction lysosomal membrane permeabilization (LMP), could overcome multiple anti-cell death mechanisms evidenced NSCLCs that responsible for failure currently used chemotherapeutic drugs. Because cardenolides bind to sodium pump, they affect signaling pathways thus have a number marked effects on tumor behavior. The aim present study was characterize vitro vivo antitumor new cardenolide (UNBS1450) experimental human NSCLCs. UNBS1450 is potent source activity case paclitaxel-and oxaliplatin-resistant subcutaneous NCI-H727 orthotopic A549 xenografts nude mice. In UNBS1450-mediated results from nonapoptotic death. mediates decrease Hsp70 at both mRNA levels, this least partly due UNBS1450-induced downregulation NFAT5/TonEBP (a factor transcriptional control Hsp70). These were paralleled by LMP, as acridine orange staining immunofluorescence analysis cathepsin B accumulation.