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Articles by T. K Kwon
Total Records ( 2 ) for T. K Kwon
  J. Y Kim , E. H Kim , S. U Kim , T. K Kwon and K. S. Choi
 

Capsaicin, a pungent ingredient of red chili peppers, has been reported to possess antitumor activities. Here, we show that subtoxic doses of capsaicin effectively sensitize multiple malignant glioma cell lines to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. Although TRAIL alone mediated partial proteolytic processing of procaspase-3 in glioma cells, cotreatment with capsaicin and TRAIL efficiently restored complete activation of caspases. We found that treatment of various gliomas with capsaicin significantly upregulated DR5, a death receptor of TRAIL, and downregulated the caspase inhibitor survivin. The induction of DR5 was mediated by CHOP/GADD153. The reduction in survivin protein level was associated with downregulation of cyclin B and Cdc2 expression, suggesting that inhibition of Cdc2 activity might contribute to capsaicin-induced survivin downregulation. Taken together, these results indicate that the activity of capsaicin toward DR5 and survivin contributes to the amplification of caspase cascades, thereby restoring TRAIL sensitivity in malignant glioma cells. Interestingly, normal astrocytes were resistant to combined treatment with capsaicin and TRAIL. Neither capsaicin-induced DR5 upregulation/survivin downregulation nor the partial processing of procaspase-3 by TRAIL was induced in astrocytes. Thus, a combined regimen using capsaicin and TRAIL may provide a safe and effective strategy for treating malignant gliomas.

  H. K Lee , M. H Song , M Kang , J. T Lee , K. A Kong , S. J Choi , K. Y Lee , H Venselaar , G Vriend , W. S Lee , H. J Park , T. K Kwon , J Bok and U. K. Kim
 

X-linked deafness type 3 (DFN3), the most prevalent X-linked form of hereditary deafness, is caused by mutations in the POU3F4 locus, which encodes a member of the POU family of transcription factors. Despite numerous reports on clinical evaluations and genetic analyses describing novel POU3F4 mutations, little is known about how such mutations affect normal functions of the POU3F4 protein and cause inner ear malformations and deafness. Here we describe three novel mutations of the POU3F4 gene and their clinical characterizations in three Korean families carrying deafness segregating at the DFN3 locus. The three mutations cause a substitution (p.Arg329Pro) or a deletion (p.Ser310del) of highly conserved amino acid residues in the POU homeodomain or a truncation that eliminates both DNA-binding domains (p.Ala116fs). In an attempt to better understand the molecular mechanisms underlying their inner ear defects, we examined the behavior of the normal and mutant forms of the POU3F4 protein in C3H/10T1/2 mesodermal cells. Protein modeling as well as in vitro assays demonstrated that these mutations are detrimental to the tertiary structure of the POU3F4 protein and severely affect its ability to bind DNA. All three mutated POU3F4 proteins failed to transactivate expression of a reporter gene. In addition, all three failed to inhibit the transcriptional activity of wild-type proteins when both wild-type and mutant proteins were coexpressed. Since most of the mutations reported for DFN3 thus far are associated with regions that encode the DNA binding domains of POU3F4, our results strongly suggest that the deafness in DFN3 patients is largely due to the null function of POU3F4.

 
 
 
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