Involvement of protein tyrosine phosphorylation and reduction of cellular sulfhydryl groups in cell death induced by 1′-acetoxychavicol acetate in Ehrlich ascites tumor cells
| Autor: | Koichi Koshimizu, Tadayoshi Hasuma, Hajime Ohigashi, David Opare Kennedy, Akira Murakami, Shuzo Otani, Akiko Kojima, Isao Matsui-Yuasa, Jerry Moffatt, Yoshihisa Yano |
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| Rok vydání: | 2002 |
| Předmět: |
Programmed cell death
Time Factors Cell Survival medicine.drug_class Lactams Macrocyclic Blotting Western Biology Toxicology Tyrosine-kinase inhibitor Acetylcysteine chemistry.chemical_compound Benzoquinones Tumor Cells Cultured medicine Animals Anticarcinogenic Agents Drug Interactions Sulfhydryl Compounds Viability assay Enzyme Inhibitors Phosphorylation Tyrosine Carcinoma Ehrlich Tumor Cytotoxicity Benzyl Alcohols Dose-Response Relationship Drug Terpenes Quinones Tyrosine phosphorylation General Medicine Glutathione Rifabutin chemistry Biochemistry Oxidation-Reduction medicine.drug |
| Zdroj: | Chemico-Biological Interactions. 139:215-230 |
| ISSN: | 0009-2797 |
| DOI: | 10.1016/s0009-2797(01)00301-5 |
| Popis: | Elucidation of the mechanisms underlying potential anticancer drugs continues and unraveling these mechanisms would not only provide a conceptual framework for drug design but also promote use of natural products for chemotherapy. To further evaluate the efficacy of the anticancer activity of 1′-acetoxychavicol acetate (ACA), this study investigates the underlying mechanisms by which ACA induces death of Ehrlich ascites tumor cells. ACA treatment induced loss of cell viability, and Western blotting analysis revealed that the compound stimulated tyrosine phosphorylation of several proteins with 27 and 70 kDa proteins being regulated in both dose- and time-dependent manner prior to loss of viability. Protein tyrosine kinase inhibitor herbimycin A moderately protected cells from ACA-induced toxicity. In addition, cellular glutathione and protein sulfydryl groups were also significantly reduced both dose- and time-dependently during evidence of cell death. Replenishing thiol levels by antioxidant, N -acetylcysteine (NAC), an excellent supplier of glutathione and precursor of glutathione, substantially recovered the viability loss, but the recovery being time-dependent, as late addition of NAC (at least 30 min after ACA addition to cultures) was, however, ineffective. Addition of NAC to ACA treated cultures also abolished tyrosine phophorylation of the 27 kDa protein. These results, at least partly, identify cellular sulfhydryl groups and protein tyrosine phosphorylation as targets of ACA cytotoxicity in tumor cells. |
| Databáze: | OpenAIRE |
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