{Reference Type}: Journal Article {Title}: Tartrolon D induces immunogenic cell death in melanoma. {Author}: Brito TL;Edson EA;Dias Florêncio KG;Machado-Neto JA;Garnique ADMB;Mesquita Luiz JP;Cunha FQ;Alves-Filho JC;Haygood M;Wilke DV; {Journal}: Chem Biol Interact {Volume}: 400 {Issue}: 0 {Year}: 2024 Sep 1 {Factor}: 5.168 {DOI}: 10.1016/j.cbi.2024.111177 {Abstract}: 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.
OBJECTIVE: This study aimed to evaluate ICD induction by TRL.
METHODS: Cell viability was evaluated by SRB assay. Cell stress, cell death, ICD features and antigen-presenting molecules were evaluated by flow cytometry and immunoblot.
RESULTS: 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.
CONCLUSIONS: 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.