Article ; Online: The marine natural product mimic MPM-1 is cytolytic and induces DAMP release from human cancer cell lines.
2022 Volume 12, Issue 1, Page(s) 15586
Abstract: Bioprospecting contributes to the discovery of new molecules with anticancer properties. Compounds with cytolytic activity and the ability to induce immunogenic cell death can be administered as intratumoral injections with the aim to activate anti-tumor ...
| Abstract | Bioprospecting contributes to the discovery of new molecules with anticancer properties. Compounds with cytolytic activity and the ability to induce immunogenic cell death can be administered as intratumoral injections with the aim to activate anti-tumor immune responses by causing the release of tumor antigens as well as damage-associated molecular patterns (DAMPs) from dying cancer cells. In the present study, we report the cytolytic and DAMP-releasing effects of a new natural product mimic termed MPM-1 that was inspired by the marine Eusynstyelamides. We found that MPM-1 rapidly killed cancer cells in vitro by inducing a necrosis-like death, which was accompanied by lysosomal swelling and perturbation of autophagy in HSC-3 (human oral squamous cell carcinoma) cells. MPM-1 also induced release of the DAMPs adenosine triphosphate (ATP) and high mobility group box 1 (HMGB1) from Ramos (B-cell lymphoma) and HSC-3 cells, as well as cell surface expression of calreticulin in HSC-3 cells. This indicates that MPM-1 has the ability to induce immunogenic cell death, further suggesting that it may have potential as a novel anticancer compound. |
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| MeSH term(s) | Adenosine Triphosphate/metabolism ; Alarmins/drug effects ; Alarmins/metabolism ; Antigens, Neoplasm ; Biological Products/pharmacology ; Calreticulin/metabolism ; Carcinoma, Squamous Cell/drug therapy ; Cell Line, Tumor ; HMGB1 Protein/drug effects ; HMGB1 Protein/metabolism ; Humans ; Mouth Neoplasms/drug therapy |
| Chemical Substances | Alarmins ; Antigens, Neoplasm ; Biological Products ; Calreticulin ; HMGB1 Protein ; Adenosine Triphosphate (8L70Q75FXE) |
| Language | English |
| Publishing date | 2022-09-16 |
| Publishing country | England |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 2615211-3 |
| ISSN | 2045-2322 ; 2045-2322 |
| ISSN (online) | 2045-2322 |
| ISSN | 2045-2322 |
| DOI | 10.1038/s41598-022-19597-4 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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