The oncolytic peptide LTX-315 induces cell death and DAMP release by mitochondria distortion in human melanoma cells
نویسندگان
چکیده
Host defense peptides (HDPs) are naturally occurring molecules found in most species, in which they play a significant role in the first line defense against intruding pathogens, and several HDPs have been shown to possess anticancer activity. Structure-activity relationship studies on the HDP bovine lactoferricin revealed a de novo design of a nonamer peptide LTX-315, with oncolytic properties. In the present study, we investigated the oncolytic activity of LTX-315 in human melanoma cells (A375). LTX-315 induced a rapid plasma membrane disruption and cell death within 2 hours. At a low concentration, fluorescence-labeled LTX-315 was internalized and accumulated in cytoplasmic vacuoles in close proximity to the mitochondria. The mitochondrial membrane potential was shown to depolarize as a consequence of LTX-315 treatment and at ultrastructural level, the mitochondria morphology was significantly altered. Release of danger signals (DAMPs) such as ATP, Cytochrome C and HMGB1 into the cell supernatant of cultured cells was evident minutes after peptide treatment. The oncolytic effect of LTX-315 involving perturbation of both the cell membrane and the mitochondria with subsequent release of DAMPs may highlight the ability of LTX-315 to induce complete regression and long-term protective immune responses as previously reported in experimental animal models.
منابع مشابه
Anticancer effect obtained against MCA205 sarcoma following treatment with the oncolytic peptide LTX-315 in combination with immune checkpoint inhibitors
Background Host defense peptides (HDPs) are naturally occurring molecules found in most eukaryotic species, in which they play a significant role in the first line of defense against pathogens. Several HDPs have shown to possess anticancer activity. Structure-anti-cancer activity relationship studies on the HDP bovine lactoferricin has resulted in the design of a short oncolytic 9-mer peptide, ...
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