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Division of Life Sciences
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Department of Chemistry
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  • [show abstract] [hide abstract]
    ABSTRACT: Aims The aim of the present study was to identify the potential therapeutic effects of BH3-mimetic gossypol on melanoma cells with acquired resistance to BRAF inhibitors. Main Methods The IC50 values of gossypol were determined using MTT assays in three melanoma cell lines with different resistance to BRAF inhibitor. The effects of gossypol on three melanoma cell lines were further examined by immunoblotting analysis, cell cycle analysis, flow cytometric apoptotic assay and autophagy assay. The functional role of autophagy in gossypol-induced growth inhibition was investigated using siRNA-mediated knockdown of Beclin-1. Key findings Gossypol retained its efficacy in BRAF-V600E melanoma clones with acquired resistance to BRAF inhibitors through a mechanism independent of MEK-ERK inhibition. Gossypol caused G2/M arrest in both BRAF mutant A375P and A375P/Mdr cells with high expression of p21Cip1, regardless of their drug resistance. Interestingly, we determined that the lack of gossypol-induced mitotic arrest in BRAF-WT-harboring SK-MEL-2 cells was associated with a low level of p21Cip1 expression. In addition, gossypol preferentially induced autophagy and apoptosis in the gossypol-sensitive cells and not in the gossypol-resistant SK-MEL-2 cells. In particular, alleviation of autophagy by knockdown of Beclin-1 partially caused a resistance to gossypol-induced cell cycle arrest at G2/M in BRAF-V600E cells with a concomitant decreased induction of apoptosis. Significance Taken together, these results suggest that gossypol may exhibit potential for the treatment of BRAF inhibitor-resistant tumors, but a functional p21Cip1 is a prerequisite for a positive response to its clinical application.
    Life sciences 01/2014;
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    ABSTRACT: The Foley catheter balloon may affect cervical ripening through changes in biochemical mediators by immunoassay and immunohistochemistry, when it is used for pre-induction cervical ripening. The aim of the study was to evaluate the changes in the biochemical mediators from the extra-amniotic space and immunohistochemistry in ripened cervical tissue after the insertion of a Foley catheter balloon (FCB) for pre-induction cervical ripening. A total of 18 pregnant women with a Bishop's score < 6, who were undergoing labour induction, were evaluated in this prospective study. The FCB was irrigated with 10 ml of phosphate buffered saline and the irrigant was collected 0, 2, 4 and 8 h after placement of the FCB or until spontaneous expulsion of the FCB occurred. Irrigant specimens were also collected from 10 spontaneous labouring (SL) women in the active phase of labour. The levels of interleukin (IL)-6, IL-8, matrix metalloproteinase (MMP)-8 and NO were measured. Cervical specimens were obtained from 12 women, including four undergoing induction; four SL and four non-pregnant (NP) women. Immunohistochemical staining was performed to localise hyaluronic acid synthase (HAS)-1, IL-6, IL-8, MMP-8, endothelial nitric oxide synthase (eNOS) and inducible NOS (iNOS). Results showed that the levels of IL-6, IL-8, and MMP-8 significantly increased over time in FCB group (p < 0.01). In the immunohistochemical analysis of cervical tissues, immunoreactivity of HAS-1 in the after FCB group was stronger than any of the other groups. The protein expressions of IL-6, IL-8, MMP-8, eNOS and iNOS were more prominent in the after FCB and SL groups than in the NP and the before FCB groups. iNOS was only observed in the after FCB and SL groups. It was concluded that FCB may affect cervical ripening through changes in biochemical mediators by immunoassay and immunohistochemistry, when it is used for pre-induction cervical ripening.
    Journal of obstetrics and gynaecology: the journal of the Institute of Obstetrics and Gynaecology 11/2013; 33(8):830-8.
  • [show abstract] [hide abstract]
    ABSTRACT: Baicalin, baicalein, and wogonin were accumulated in hairy roots derived from Scutellaria lateriflora and Scutellaria baicalensis. The levels of baicalein and baicalin were 6.8 and 5.0 times higher, respectively, in S. baicalensis than in S. lateriflora. A total of 47 metabolites were detected and identified in Scutellaria species by GC-TOF MS. The metabolites from the two species were subjected to principal component analysis (PCA) to evaluate differences. PCA fully distinguished between the two species. The results showed that individual phenolic acids and phenylalanine, precursors for the phenylpropanoid biosynthetic pathway, were higher in S. baicalensis than in S. lateriflora. This GC-TOF MS-based metabolic profiling approach was a viable alternative method to differentiate metabolic profiles between species.
    World Journal of Microbiology and Biotechnology 10/2013;


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Physical Chemistry Chemical Physics 12/2011; 14(4):1480-4.
IEEE Transactions on Electron Devices 01/2003;

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