Multitargeting Prodrugs that Release Oxaliplatin, Doxorubicin and Gemcitabine are Potent Inhibitors of Tumor Growth and Effective Inducers of Immunogenic Cell Death
Language English Country Germany Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
- Keywords
- Doxorubicin, Gemcitabine, Immunogenic Cell Death, Multi-Targeting Prodrugs, Oxaliplatin,
- MeSH
- Doxorubicin pharmacology therapeutic use MeSH
- Gemcitabine MeSH
- Immunogenic Cell Death MeSH
- Humans MeSH
- Mice MeSH
- Cell Line, Tumor MeSH
- Neoplasms * MeSH
- Oxaliplatin pharmacology MeSH
- Prodrugs * pharmacology therapeutic use MeSH
- Antineoplastic Agents * pharmacology therapeutic use MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Doxorubicin MeSH
- Gemcitabine MeSH
- Oxaliplatin MeSH
- Prodrugs * MeSH
- Antineoplastic Agents * MeSH
A multitargeting prodrug (2) that releases gemcitabine, oxaliplatin, and doxorubicin in their active form in cancer cells is a potent cytotoxic agent with nM IC50s ; it is highly selective to cancer cells with mean selectivity indices to human (136) and murine (320) cancer cells. It effectively induces release of DAMPs (CALR, ATP & HMGB1) in CT26 cells facilitating more efficient phagocytosis by J774 macrophages than the FDA drugs or their co-administration. The viability of CT26 cells co-cultured with J774 macrophages and treated with 2 was reduced by 32 % compared to the non-treated cells, suggesting a synergistic antiproliferative effect between the chemical and immune reactions. 2 inhibited in vivo tumor growth in two murine models (LLC and CT26) better than the FDA drugs or their co-administration with significantly lower body weight loss. Mice inoculated with CT26 cells treated with 2 showed slightly better tumor free survival than doxorubicin.
Czech Academy of Sciences Institute of Biophysics Kralovopolska 135 61200 Brno Czech Republic
Department of Biophysics Palacky University Slechtitelu 27 783 71 Olomouc Czech Republic
Dipartimento di Scienze del Farmaco Universita di Padova 35131 Padova Italy
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