Induction of p53‐independent growth inhibition in lung carcinoma cell A549 by gypenosides
| Autor: | Jinn-Shyan Wang, Wei-Chih Chao, Bing-Huei Chen, Jyh-Feng Lu, Li-Ju Lin, Baskaran Stephen Inbaraj, Tzu-Hsuan Chiang, Jung-Sen Liu |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Chlorophyll
Lung Neoplasms Cyclin A Apoptosis Mass Spectrometry chemistry.chemical_compound Cell Line Tumor Humans Annexin A5 lung cancer cell IC50 saponin Chromatography High Pressure Liquid Cell Proliferation A549 cell biology Plant Extracts Cell growth Gynostemma pentaphyllum Cell Cycle Original Articles Cell Biology Saponins Cell cycle Flow Cytometry biology.organism_classification Carotenoids carotenoid Gynostemma chemistry Biochemistry biology.protein Molecular Medicine Tumor Suppressor Protein p53 Growth inhibition |
| Zdroj: | Journal of Cellular and Molecular Medicine |
| ISSN: | 1582-4934 1582-1838 |
| DOI: | 10.1111/jcmm.12546 |
| Popis: | The objectives of this study are to investigate antiproliferative effect and mechanisms of bioactive compounds from Gynostemma pentaphyllum (G. pentaphyllum) on lung carcinoma cell A549. Saponins, carotenoids and chlorophylls were extracted and fractionated by column chromatography, and were subjected to high-performance liquid chromatography-mass spectrometry analyses. The saponin fraction, which consisted mainly of gypenoside (Gyp) XXII and XXIII, rather than the carotenoid and chlorophyll ones, was effective in inhibiting A549 cell growth in a concentration- and a time-dependent manner as evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The estimated half maximal inhibitory concentration (IC50 ) of Gyp on A549 cells was 30.6 μg/ml. Gyp was further demonstrated to induce an apparent arrest of the A549 cell cycle at both the S phase and the G2/M phase, accompanied by a concentration- and a time-dependent increase in the proportions of both the early and late apoptotic cells. Furthermore, Gyp down-regulated cellular expression of cyclin A and B as well as BCL-2, while up-regulated the expression of BAX, DNA degradation factor 35 KD, poly [ADP-ribose] polymerase 1, p53, p21 and caspase-3. Nevertheless, both the treatment of a p53 inhibitor, pifithrin-α, and the small hairpin RNA-mediated p53 knockdown in the A549 cells did not alter the growth inhibition effect induced by Gyp. As a result, the cell cycle arrest and apoptosis of A549 cells induced by Gyp would most likely proceed through p53-independent pathway(s). |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text