• Proceedings of the PSK Conference
• /
• 2002.10a
• /
• pp.319.1-319.1
• /
• 2002

Yomogin. an eudesmane sesquiterpene isolated from Artemisia princeps, was found to induce apoptosis in human promyelocytic leukaemia, HL -60 cell with characteristic apoptotic features like nuclear condensation, apoptotic body formation, flipping of membrane phosphatidylserine, release of mitochondrial cytochrome c and caspase-8. -9. and -3 activation. Furthermore. early yomogin-induced cytochrome c release was not affected by the caspase inhibitor Z-VAd fmk and preceded loss of mitochondrial membrane potential. The results suggest that induction of apoptosis by yomogin may provide a pivotal mechanism for their cancer chemopreventive function.

• Journal of Applied Biological Chemistry
• /
• v.66
• /
• pp.53-59
• /
• 2023

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has no effect on normal cells, but selectively can induce apoptosis in tumor cells. Gartanin, a xanthone compound in mangosteen, has been shown to inhibit cancer cell growth by arresting the cell cycle and inducing autophage. In this study, we revealed that gartanin can sensitize TRAIL-induced human liver cancer cell death. We also found that gartanin enhances DR5 expression, a death receptor for TRAIL. This effect appears to be related to CHOP activation associated with the response of endoplasmic reticulum stress. Gartanin treatment also inhibited p62 protein expression and cleaved LC3 to activate autophagy flux, which is related with TRAIL-induced cell death. Pretreatment with autophagy flux inhibitor, LY294002, inhibited gartanin-induced DR5 expression. In summary, our results reveal that the combined treatment of gartanin and TRAIL can be a valuable tool for cancer treatment.

• Proceedings of the Korean Society for Applied Microbiology Conference
• /
• 2003.06a
• /
• pp.117-118
• /
• 2003

• Proceedings of the PSK Conference
• /
• 2001.04a
• /
• pp.104-104
• /
• 2001

• Proceedings of the Korea Environmental Mutagen Society Conference
• /
• 2004.11a
• /
• pp.140-140
• /
• 2004

• Proceedings of the Zoological Society Korea Conference
• /
• 1999.10b
• /
• pp.198.2-198
• /
• 1999

No Abstract, See Full Text

• Tuberculosis and Respiratory Diseases
• /
• v.65 no.6
• /
• pp.476-486
• /
• 2008

Background: TRAIL (TNF-related apoptosis inducing ligand) is a newly identified member of the TNF gene family which appears to have tumor-selective cytotoxicity due to the distinct decoy receptor system. TRAIL has direct access to caspase machinery and induces apoptosis regardless of p53 phenotype. Therefore, TRAIL has a therapeutic potential in lung cancer which frequently harbors p53 mutation in more than 50% of cases. However, it was shown that TRAIL also could activates $NF-{\kappa}B$ in some cell lines which might inhibit TRAIL-induced apoptosis. This study was designed to investigate whether TRAIL can activate $NF-{\kappa}B$ in lung cancer cell lines relatively resistant to TRAIL-induced apoptosis and inhibition of $NF-{\kappa}B$ activation using proteasome inhibitor MG132 which blocks $I{\kappa}B{\alpha}$ degradation can sensitize lung cancer cells to TRAIL-induced apoptosis. Methods: A549 (wt p53) and NCI-H1299 (null p53) lung cancer cells were used and cell viability test was done by MTT assay. Apoptosis was confirmed with Annexin V assay followed by FACS analysis. To study $NF-{\kappa}B$-dependent transcriptional activation, a luciferase reporter gene assay was used after making A549 and NCI-H1299 cells stably transfected with IgG ${\kappa}-NF-{\kappa}B$ luciferase construct. To investigate DNA binding of $NF-{\kappa}B$ activated by TRAIL, electromobility shift assay was used and supershift assay was done using anti-p65 antibody. Western blot was done for the study of $I{\kappa}B{\alpha}$ degradation. Results: A549 and NCI-H1299 cells were relatively resistant to TRAIL-induced apoptosis showing only 20~30% cell death even at the concentration 100 ng/ml, but MG132 ($3{\mu}M$) pre-treatment 1 hour prior to TRAIL addition greatly increased cell death more than 80%. Luciferase assay showed TRAIL-induced $NF-{\kappa}B$ transcriptional activity in both cell lines. Electromobility shift assay demonstrated DNA binding complex of $NF-{\kappa}B$ activated by TRAIL and supershift with p65 antibody. $I{\kappa}B{\alpha}$ degradation was proven by western blot. MG132 completely blocked both TRAIL-induced $NF-{\kappa}B$ dependent luciferase activity and DNA binding of $NF-{\kappa}B$. Conclusion: This results suggest that inhibition of $NF-{\kappa}B$ can be a potentially useful strategy to enhance TRAIL-induced tumor cell killing in lung cancer.

• Journal of Life Science
• /
• v.19 no.7
• /
• pp.871-877
• /
• 2009

We investigated the effects of sodium butyrate, a histone deacetylase inhibitor, on the cell cycle progression in human monocytic leukemia U937 cells. Exposure of U937 cells to sodium butyrate resulted in growth inhibition, G1 arrest of the cell cycle and induction of apoptosis in a dose-dependent manner as measured by MTT assay and flow cytometry analysis. The increase in G1 arrest was associated with the down-regulation in cyclin D1, E, A, cyclin-dependent kinase (Cdk) 4 and 6 expression, and up-regulation of Cdk inhibitors such as p21 and p27. Sodium butyrate treatment also inhibited the phosphorylation of retinoblastoma protein (pRB) and p130, however, the levels of transcription factors E2F-1 and E2F-4 were not markedly modulated. Furthermore, the down-regulation of phosphorylation of pRB and p130 by this compound was associated with enhanced binding of pRB and E2F-1, as well as p130 and E2F-4, respectively. Overall, the present results demonstrate a combined mechanism involving the inhibition of pRBjp130 phosphorylation and induction of Cdk inhibitors as targets for sodium butyrate that may explain some of its anti-cancer effects in U937 cells.

• Tuberculosis and Respiratory Diseases
• /
• v.58 no.5
• /
• pp.480-489
• /
• 2005

Background : Dysregulation of apoptosis plays an important role in carcinogenesis, tumor progression, and resistance to chemotherapy. X-linked inhibitor of apoptosis (XIAP) is considered to be the most potent caspase inhibitor of all known IAP (inhibitor of apoptosis) family members. This study was designed to assess the pattern of expression and the prognostic value of XIAP in radically resected non-small cell lung carcinoma (NSCLC) patients. Method : The expression of XIAP and its relationship with clinicopathologic parameters (patient age, TNM stage, TNM-pT, TNM-pN, histologic type, VEGF expression, microvessel density, PCNA index) and overall survival were analysed with formalin-fixed, paraffin-embedded blocks from eighty cases of NSCLC. In addition, the apoptotic index (AI) was also assessed. Results : In a regard to histologic type, squamous cell carcinoma (SCC) showed XIAP expression in 91.3%(42/46) and adenocarcinoma (AC) in 61.8%(21/34). The difference was significant(p=0.001). There was no correlation between XIAP expression and other parameters. In the group of AC, XIAP expression showed the signifcant correlation with older age group ${\geq}58years$ and VEGF expression(p=0.028, p=0.014, respectively). The AI in the group with or without XIAP expression were $2.5{\pm}4.9%$ and $18.5{\pm}28.9%$, respectively(p=0.001). Both groups just aforementioned showed no significant difference in median survival time (42.5 months, 29.8 months, respectively). Conclusion : This study suggests that the XIAP expression in NSCLCs could have relation to inhibition of apoptosis, and show differential expression according to histologic type. However, its prognostic role during the progression of NSCLC needs to be further defined.

• Biomedical Science Letters
• /
• v.19 no.2
• /
• pp.118-123
• /
• 2013

Tumor necrosis factor-alpha (TNF-${\alpha}$) is a proinflammatory cytokine that mediates the inflammatory response and immune functions, and modulates the proliferation, differentiation and cell death of cancer cells. The differential functions of TNF-${\alpha}$ in various human cells due to the formation of different stimulating pathway upon the binding of TNF-${\alpha}$ to its receptors. In the present study, we examined the different effects of TNF-${\alpha}$ on the survival and apoptosis between normal granulocytes and human myeloid leukemia HL-60 cells. Although TNF-${\alpha}$ did not affect on the constitutive apoptosis of granulocytes, TNF-${\alpha}$ strongly induced the apoptosis of HL-60 cells in a dose- and a time-dependent manner. TNF-${\alpha}$-induced apoptosis was occurred via the activation of caspase 8, caspase 9 and caspase 3/7 and the induction of ROS production in HL-60 cells. Also, BAY-11-7085, a NF-${\kappa}B$ inhibitor, blocked the TNF-${\alpha}$-induced apoptosis in HL-60 cells. NF-${\kappa}B$ may be involved in TNF-${\alpha}$-induced apoptotic signaling pathway in HL-60 cells. These results suggest that TNF-${\alpha}$ activates apoptotic pathways and its process depends on cell type and many cellular factors. A better understanding of the differential effect of TNF-${\alpha}$ on cell apoptosis and survival may provide important information that can be used to elucidate the specific inhibitory effect of TNF-${\alpha}$ on the cancer dis.