title: Aloe-emodin induces apoptosis of human nasopharyngeal carcinoma cells via caspase-8-mediated activation of the mitochondrial death pathway.
abstract: 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.
authors: Department of Medical Laboratory Science and Biotechnology, Central Taiwan University of Science and Technology, Taichung, Taiwan.
authors: Meng-Liang
authors: ML
authors: Lin
authors: Yao-Cheng
authors: YC
authors: Lu
authors: Jing-Gung
authors: JG
authors: Chung
authors: Yi-Chen
authors: YC
authors: Li
authors: Shyang-Guang
authors: SG
authors: Wang
authors: Sue-Hwee
authors: SH
authors: N G
authors: Chia-Yin
authors: CY
authors: Wu
authors: Hong-Lin
authors: HL
authors: Su
authors: Shih-Shun
authors: SS
authors: Chen
mesh_terms: D000880:Anthraquinones / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D016203:CDC2 Protein Kinase; D053148:Caspase 3 / Q000502:physiology; D053181:Caspase 8 / Q000502:physiology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D019926:Cyclin B / Q000378:metabolism; D056744:Cyclin B1 / Q000378:metabolism; D018844:Cyclin-Dependent Kinases; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000502:physiology; D051020:bcl-X Protein / Q000502:physiology
chemical_list: D000880:Anthraquinones; C494826:BAX protein, human; C494811:BCL2L1 protein, human; C534699:CCNB1 protein, human; D019926:Cyclin B; D056744:Cyclin B1; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; C518327:aloe emodin; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human; D018844:Cyclin-Dependent Kinases; D053148:Caspase 3; D053181:Caspase 8