Ethyl pyruvate administration inhibits hepatic tumor growth
| العنوان: | Ethyl pyruvate administration inhibits hepatic tumor growth |
|---|---|
| المؤلفون: | Donna Beer-Stolz, Herbert J. Zeh, Andrew A. Amoscato, Nicole E. Schapiro, Antonio Romo de Vivar Chavez, Michael T. Lotze, Patricia Loughran, Michael E. de Vera, Stephen H. Thorne, Xiaoyan Liang |
| المصدر: | Journal of Leukocyte Biology. 86:599-607 |
| بيانات النشر: | Oxford University Press (OUP), 2009. |
| سنة النشر: | 2009 |
| مصطلحات موضوعية: | medicine.medical_specialty, Time Factors, Liver tumor, Cell Survival, Injections, Subcutaneous, Genetic Vectors, Immunology, Cell, Poly (ADP-Ribose) Polymerase-1, Apoptosis, Inflammation, Pharmacology, Biology, Transfection, Mice, Random Allocation, Liver Neoplasms, Experimental, Immune system, Genes, Reporter, Transduction, Genetic, Cell Line, Tumor, Internal medicine, medicine, Animals, Immunology and Allergy, HMGB1 Protein, Pyruvates, B cell, Cell Proliferation, Luciferases, Renilla, Dose-Response Relationship, Drug, Interleukin-6, Lentivirus, Antibodies, Monoclonal, Cancer, Cell Biology, medicine.disease, Tumor Burden, Mice, Inbred C57BL, Endocrinology, medicine.anatomical_structure, Fluorescent Antibody Technique, Direct, Cell culture, Female, Poly(ADP-ribose) Polymerases, medicine.symptom, Colorectal Neoplasms, Microtubule-Associated Proteins |
| الوصف: | The first demonstration of ethyl pyruvate inhibition of liver tumor growth associated with induction of tumor apoptosis, diminished HMGB1 release, and decreased inflammation is reported. EP is a potent inhibitor of HMGB1 release that has significant anti–inflammatory activities and exerts a protective effect in animal models of inflammation. As inflammation is linked to cancer growth, we hypothesized that EP would have anti–tumor activity and explored its effects in a liver tumor model. Mice injected intraportally with MC38 colorectal cancer cells led to the growth of visible hepatic tumors within 2 weeks. Pretreatment with EP 30 min prior to infusion of tumor cells and continuing daily for 9 days inhibited tumor growth significantly in a dose–dependent manner, with 80 mg/kg EP achieving >70% reduction in the number of tumor nodules when compared with untreated animals. Delayed treatment with EP also suppressed tumor growth significantly, although to a lesser extent. Tumors had early, marked leukocytic infiltrates, and EP administration decreased innate (NK cells, monocytes) and adaptive (T and B cell lymphocytic) immune cell infiltrates acutely and significantly in the liver. Serum IL–6 and HMGB1 levels, which were elevated following tumor injection, were decreased significantly in EP–treated animals. Tumors showed an increase in apoptosis in EP–treated mice, and tumor cells treated in vitro with EP had marked increases in LC3–II and cleaved PARP, consistent with enhanced autophagic flux and apoptosis. Thus, EP inhibition of tumor growth in the liver was mediated by tumor (induction of apoptosis) and host (decreased inflammation) effects. EP administration may have a therapeutic role in the treatment of cancer in conjunction with other therapeutic agents. |
| تدمد: | 1938-3673 0741-5400 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0f4894d2740f2ec03537e1140ae4e18bTest https://doi.org/10.1189/jlb.0908578Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....0f4894d2740f2ec03537e1140ae4e18b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19383673 07415400 |
|---|