Raptinal Induces Gasdermin E-Dependent Pyroptosis in Naive and Therapy-Resistant Melanoma.

ABSTRACT: Lack of response and acquired resistance continue to be limitations of targeted and immune-based therapies. Pyroptosis is an inflammatory form of cell death characterized by the release of inflammatory damage-associated molecular patterns (DAMP) and cytokines via gasdermin (GSDM) protein pores in the plasma membrane. Induction of pyroptosis has implications for treatment strategies in both therapy-responsive, as well as resistance forms of melanoma. We show that the caspase-3 activator, raptinal, induces pyroptosis in both human and mouse melanoma cell line models and delays tumor growth in vivo. Release of DAMPs and inflammatory cytokines was dependent on caspase activity and GSDME expression. Furthermore, raptinal stimulated pyroptosis in melanoma models that have acquired resistance to

SUBMITTER: Vernon M 

PROVIDER: S-EPMC9722513 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature