Publication date: Aug 02, 2024
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. This study aimed to evaluate ICD induction by TRL. Cell viability was evaluated by SRB assay. Cell stress, cell death, ICD features and antigen-presenting molecules were evaluated by flow cytometry and immunoblot. 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 (IC) ranging from 0. 03 μM to 13 μM. Metastatic melanomas, SK-MEL-28, B16-F10, and WM293A, were more sensitive cell lines, with IC 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. 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.
Concepts | Keywords |
---|---|
Degrading | Antitumor immune response |
F10 | Damage-associated molecular patterns |
Mice | Marine natural products |
Teredinibacter | Metastatic melanoma |
Tumor |
Semantics
Type | Source | Name |
---|---|---|
disease | MESH | endoplasmic reticulum stress |
pathway | KEGG | Autophagy |
pathway | KEGG | Apoptosis |
drug | DRUGBANK | Honey |
disease | MESH | Tumor |
drug | DRUGBANK | Tropicamide |
drug | DRUGBANK | Microcrystalline cellulose |
pathway | KEGG | Melanoma |
disease | MESH | melanoma |