Aloe-emodin induces apoptosis of human nasopharyngeal carcinoma cells via caspase-8-mediated activation of the mitochondrial death pathway
| Autor: | Shyang-Guang Wang, Shih-Shun Chen, Meng Liang Lin, Yi-Chen Li, Chia-Yin Wu, Hong-Lin Su, Jing Gung Chung, Sue-Hwee Ng, Yao-Cheng Lu |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Cancer Research
Programmed cell death Poly ADP ribose polymerase bcl-X Protein Anthraquinones Apoptosis Cyclin B Caspase 8 Cell Line Tumor CDC2 Protein Kinase Humans FADD Cyclin B1 bcl-2-Associated X Protein biology Caspase 3 Cytochrome c Cell Cycle Nasopharyngeal Neoplasms Molecular biology Cyclin-Dependent Kinases Mitochondria Cell biology Oncology biology.protein DNA fragmentation Apoptosis-inducing factor Reactive Oxygen Species |
| Zdroj: | Cancer Letters. 291:46-58 |
| ISSN: | 0304-3835 |
| DOI: | 10.1016/j.canlet.2009.09.016 |
| Popis: | Aloe-emodin (AE), a natural, biologically active compound from the rhizome of Rheum palmatum, has been shown to induce apoptosis in several cancer cell lines in vitro. However, its molecular mechanism of action in the apoptosis induction of human nasopharyngeal carcinoma (NPC) cells has not been explored. This study shows that AE induced G(2)/M phase arrest by increasing levels of cyclin B1 bound to Cdc2, and also caused an increase in apoptosis of NPC cells, which was characterized by morphological changes, nuclear condensation, DNA fragmentation, caspase-3 activation, cleavage of poly (ADP-ribose) polymerase (PARP) and increased sub-G(1) population. Treatment of NPC cells with AE also resulted in a decrease in Bcl-X(L) and an increase in Bax expression. Ectopic expression of Bcl-X(L) but not Bcl-2 or small interfering RNA (siRNA)-mediated attenuation of Bax suppressed AE-induced apoptotic cell death. AE-induced loss of mitochondrial membrane potential (MMP) and increase in cellular Ca(++) content, reactive oxygen species (ROS) and apoptotic cell death were suppressed by the treatment of cyclosporin A (CsA) or caspase-8 inhibitor Z-IETD-FMK. Co-treatment with caspase-9 inhibitor Z-LEHD-FMK could inhibit AE-induced cell death and the activation of caspase-3 and -9. In addition, suppression of caspase-8 with the specific inhibitor Z-IETD-FMK inhibited AE-induced the activation of Bax, the cleavage of Bid, the translocation of tBid to the mitochondria and the release of cytochrome c, apoptosis-inducing factor (AIF) and Endo G from the mitochondria and subsequent apoptosis. Taken together, these results indicate that the caspase-8-mediated activation of the mitochondrial death pathway plays a critical role in AE-induced apoptosis of NPC cells. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect