Apigenin potentiates the antitumor activity of 5-FU on solid Ehrlich carcinoma: Crosstalk between apoptotic and JNK-mediated autophagic cell death platforms
| Autor: | Hanaa H. Gaballah, Darin A. Mohamed, Rasha A. Gaber |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Antimetabolites Antineoplastic Programmed cell death Proliferation index MAP Kinase Kinase 4 Flavonoid Apoptosis Pharmacology Toxicology Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Antineoplastic Combined Chemotherapy Protocols Animals Apigenin Carcinoma Ehrlich Tumor Caspase chemistry.chemical_classification Cell Death biology Glutathione peroxidase Drug Synergism Malondialdehyde Xenograft Model Antitumor Assays Tumor Burden Ki-67 Antigen 030104 developmental biology chemistry 030220 oncology & carcinogenesis biology.protein Myeloid Cell Leukemia Sequence 1 Protein Fluorouracil |
| Zdroj: | Toxicology and Applied Pharmacology. 316:27-35 |
| ISSN: | 0041-008X |
| DOI: | 10.1016/j.taap.2016.12.012 |
| Popis: | Background Although 5- Fluorouracil (5-FU) has exhibited effectiveness against cancer, novel therapeutic strategies are needed to enhance its antitumor efficiency and modulate its cytotoxity. Apigenin, a flavonoid present in fruits and vegetables, is a potent dietary phytochemical effective in cancer chemoprevention. Aim This study was undertaken to investigate the potential synergistic antitumor activity of apigenin and 5-FU on Solid Ehrlich carcinoma (SEC). Methods Eighty Swiss albino male mice were divided into four equal groups: vehicle treated control SEC, SEC + 5-FU, SEC + apigenin, SEC + 5-FU + apigenin. Beclin-1 and caspases 3, 9 and JNK activities were estimated by ELISA; mRNA expression levels of the antiapoptotic gene Mcl-1 were estimated using quantitative real-time RT-PCR, while tissue malondialdehyde (MDA), glutathione peroxidase and total antioxidant capacity were evaluated spectrophotometrically. A part of the tumor was examined for histopathological and Ki-67 immunohistochemistry analysis. Results 5-FU and/or apigenin caused significant increase in tissue levels of Beclin-1, caspases 3, 9 and JNK activities, MDA with significant decrease in tumor volume, Mcl-1expression, tissue glutathione peroxidase and total antioxidant capacity and alleviated the histopathological changes with significant decrease of Ki-67 proliferation index compared to vehicle treated SEC control group. In conclusion The combination of 5-FU and apigenin had a greater effect than each of 5-FU or apigenin alone against solid Ehrlich carcinoma in mice. |
| Databáze: | OpenAIRE |
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