AIMS: Grandinin (C(46)H(34)O(30)) is a compound found in Melaleuca quinquenervia leaves and in oaks. This study is to determine effects of grandinin on malignant lung cells and the related molecular mechanisms. METHODS: Malignant cells were treated with grandinin with various concentrations. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrozolium bromide (MTT) assays and apoptosis assays were performed to determine effects of grandinin on cell viability and apoptosis. Western blotting and real time-PCR were used to determine if grandinin affects levels of phosphorylated EGFR (p-EGFR) and phosphorylated AKT (p-AKT), as well as their mRNA transcript levels. RESULTS: It was found that grandinin treatments reduce viability of malignant lung cells and induces apoptosis. When treated with grandinin (16 μM), the apoptosis of the three lung cancer cell lines MS-1, A549, and LK-2 were increased by 8-9 folds, in comparison with the cells treated with DMSO only (the control condition). Furthermore, grandinin treatments lead to down-regulation of levels of p-EGFR and p-AKT in three malignant lung cell lines. However, grandinin does not affect mRNA levels of EGFR and AKT. CONCLUSIONS: These experimental results indicated grandinin significantly reduce malignant cell viability and effectively induces apoptosis of malignant lung cells by mediating phosphorylation down-regulation of cellular signaling proteins EGFR and AKT. It is suggested that grandinin treatments might be an effective therapeutic strategy of lung malignancies upon further studies in the future.
AIMS: Grandinin (C(46)H(34)O(30)) is a compound found in Melaleuca quinquenervia leaves and in oaks. This study is to determine effects of grandinin on malignant lung cells and the related molecular mechanisms. METHODS: Malignant cells were treated with grandinin with various concentrations. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrozolium bromide (MTT) assays and apoptosis assays were performed to determine effects of grandinin on cell viability and apoptosis. Western blotting and real time-PCR were used to determine if grandinin affects levels of phosphorylated EGFR (p-EGFR) and phosphorylated AKT (p-AKT), as well as their mRNA transcript levels. RESULTS: It was found that grandinin treatments reduce viability of malignant lung cells and induces apoptosis. When treated with grandinin (16 μM), the apoptosis of the three lung cancer cell lines MS-1, A549, and LK-2 were increased by 8-9 folds, in comparison with the cells treated with DMSO only (the control condition). Furthermore, grandinin treatments lead to down-regulation of levels of p-EGFR and p-AKT in three malignant lung cell lines. However, grandinin does not affect mRNA levels of EGFR and AKT. CONCLUSIONS: These experimental results indicated grandinin significantly reduce malignant cell viability and effectively induces apoptosis of malignant lung cells by mediating phosphorylation down-regulation of cellular signaling proteins EGFR and AKT. It is suggested that grandinin treatments might be an effective therapeutic strategy of lung malignancies upon further studies in the future.
Authors: Mohamed S A Marzouk; Fatma A Moharram; Mona A Mohamed; Amira M Gamal-Eldeen; Elsayed A Aboutabl Journal: Z Naturforsch C J Biosci Date: 2007 Jul-Aug