%0 Journal Article
%T Tartrolon D induces immunogenic cell death in melanoma.
%A Brito TL
%A Edson EA
%A Dias Florêncio KG
%A Machado-Neto JA
%A Garnique ADMB
%A Mesquita Luiz JP
%A Cunha FQ
%A Alves-Filho JC
%A Haygood M
%A Wilke DV
%J Chem Biol Interact
%V 400
%N 0
%D 2024 Sep 1
%M 39097071
%F 5.168
%R 10.1016/j.cbi.2024.111177
%X Tartrolon D (TRL) is produced by Teredinibacter turnerae, a symbiotic cellulose-degrading bacteria in shipworm gills. Immunogenic cell death (ICD) induction contributes to a better and longer-lasting response to anticancer treatment. Tumor cells undergoing ICD trigger activation of the immune system, as a vaccine.<BR><B>OBJECTIVE: </B>This study aimed to evaluate ICD induction by TRL.<BR><B>METHODS: </B>Cell viability was evaluated by SRB assay. Cell stress, cell death, ICD features and antigen-presenting molecules were evaluated by flow cytometry and immunoblot.<BR><B>RESULTS: </B>TRL showed antiproliferative activity on 7 tumor cell lines (L929, HCT 116, B16-F10, WM293A, SK-MEL-28, PC-3M, and MCF-7) and a non-tumor cell (HEK293A), with an inhibition concentration mean (IC50) ranging from 0.03 μM to 13 μM. Metastatic melanomas, SK-MEL-28, B16-F10, and WM293A, were more sensitive cell lines, with IC50 ranging from 0.07 to 1.2 μM. TRL induced apoptosis along with autophagy and endoplasmic reticulum stress and release of typical damage-associated molecular patterns (DAMPs) of ICD such calreticulin, ERp57, and HSP70 exposure, and HMGB1 release. Additionally, melanoma B16-F10 exposed to TRL increased expression of antigen-presenting molecules MHC II and CD1d and induced activation of splenocytes of C57BL/6 mice.<BR><B>CONCLUSIONS: </B>In spite of recent advances provided by target therapy and immunotherapy, advanced metastatic melanoma is incurable for more than half of patients. ICD inducers yield better and long-lasting responses to anticancer treatment. Our findings shed light on an anticancer candidate of marine origin that induces ICD in melanoma.