Chemopreventive effect of α-hederin/carboplatin combination against experimental colon hyperplasia and impact on JNK signaling
| Autor: | Attia M. Gabr, Nema Soliman, Sawsan A. Zaitone, Amal M. Youssef, Hoda S. Elmahdi, Mohamed El-Sherbiny, Afaf T Ibrahiem, Alaaeldeen M. Elbahaie, Hoda I. Bahr |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Male
Colon Colorectal cancer Health Toxicology and Mutagenesis Apoptosis 010501 environmental sciences Toxicology 01 natural sciences Carboplatin Mice Phosphatidylinositol 3-Kinases 03 medical and health sciences chemistry.chemical_compound medicine Animals Oleanolic Acid 0105 earth and related environmental sciences Triterpenoid saponin chemistry.chemical_classification 0303 health sciences Hyperplasia α hederin business.industry 030302 biochemistry & molecular biology Cancer medicine.disease 1 2-Dimethylhydrazine carbohydrates (lipids) chemistry Colonic Neoplasms Cancer research business human activities |
| Zdroj: | Toxicology Mechanisms and Methods. 31:138-149 |
| ISSN: | 1537-6524 1537-6516 |
| DOI: | 10.1080/15376516.2020.1849483 |
| Popis: | Colon cancer is the commonest cancer worldwide. α-Hederin is a monodesmosidic triterpenoid saponin possessing diverse pharmacological activities. The running experiment was designed to test the chemopreventive activity of α-hederin when used as an adjuvant to carboplatin in an experimental model of mouse colon hyperplasia induced by 1,2-dimethylhydrazine (DMH). Fifty male Swiss albino mice were classified into five groups: group (I): saline group, group (II): DMH-induced colon hyperplasia control group, group (III): DMH + carboplatin (5 mg/kg) group, group (IV): DMH + α-hederin (80 mg/kg) group, and group (V): DMH + carboplatin (5 mg/kg)+α-hederin (80 mg/kg) group. Analyzing of colonic tissue indicated that the disease control group showed higher colon levels of phospho-PI3K to total-PI3K, phospho-AKT to total-AKT and cyclin D1 concurrent with lower phospho-JNK/total JNK ratio and caspase 3. However, treatment with α-hederin, in combination with carboplatin, favorably ameliorated phosphorylation of PI3K/AKT/JNK proteins, increased colon caspase 3 and downregulated cyclin D1. Microscopically, α-hederin, in combination with carboplatin, produced the most reduction in the histologic hyperplasia score, enhanced the goblet cell survival in periodic acid Schiff staining and reduced proliferation (Ki-67 immunostaining) in the current colon hyperplasia model. Collectively, the current study highlighted for the first time that using α-hederin as an adjuvant to carboplatin enhanced its chemopreventive activity, improved JNK signaling and increased apoptosis. Hence, further studies are warranted to test α-hederin as a promising candidate with chemotherapeutic agents in treating colon cancer. |
| Databáze: | OpenAIRE |
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