Oh D.,Oral Biology Research Institute |
Yim M.-J.,Regional Innovation Center for Dental Science and Engineering |
Park J.-J.,Regional Innovation Center for Dental Science and Engineering |
Kang K.-R.,Oral Biology Research Institute |
And 12 more authors.
Oncology Reports | Year: 2015
In the present study, we examined the anticancer properties of berberine in KB oral cancer cells with a specific focus on its cellular mechanism. Berberine did not affect the cell viability of the primary human normal oral keratinocytes that were used as a control. However, the viability of KB cells was found to decrease significantly in the presence of berberine in a dose-dependent manner. Furthermore, in KB cells, berberine induced the fragmentation of genomic DNA, changes in cell morphology, and nuclear condensation. In addition, caspase-3 and -7 activation, and an increase in apoptosis were observed. Berberine was also found to upregulate significantly the expression of the death receptor ligand, FasL. In turn, this upregulation triggered the activation of pro-apoptotic factors such as caspase-8, -9 and -3 and poly(ADP-ribose) polymerase (PARP). Furthermore, pro-apoptotic factors such as Bax, Bad and Apaf-1 were also significantly upregulated by berberine. Anti-apoptotic factors such as Bcl-2 and Bcl-xL were downregulated. Z-VAD-FMK, a cell-permeable pan-caspase inhibitor, suppressed the activation of caspase-3 and PARP. These results clearly indicate that berberine-induced cell death of KB oral cancer cells was mediated by both extrinsic death receptor-dependent and intrinsic mitochondrial-dependent apoptotic signaling pathways. In addition, berberine-induced upregulation of FasL was shown to be mediated by the p38 MAPK signaling pathway. We also found that berberine-induced migration suppression was mediated by downregulation of MMP-2 and MMP-9 through phosphorylation of p38 MAPK. In summary, berberine has the potential to be used as a chemotherapeutic agent, with limited side-effects, for the management of oral cancer.
Seo Y.-J.,Chosun University |
Lee I.-K.,Chosun University |
Jang H.-S.,Oral Biology Research Institute
Tissue Engineering and Regenerative Medicine | Year: 2013
Periodontal ligament fibroblasts (PDLFs) are essential to most periodontal tissue regeneration processes. This study evaluated the potential of fibroblast growth factor (FGF) and PDLF-conditioned media to modulate fibroblast differentiation from bone marrow stromal cells (BMSCs) that were obtained from mongrel dogs. The medium obtained from culture of periodontal ligament fibroblasts of dogs was used for the PDLF-conditioned media. In the control group, the BMSCs were only cultured without FGF and PDLF-conditioned media. In experimental group 1, the BMSCs were loaded with FGF (3 ng/mL). In experimental group 2, the BMSCs were treated with PDLF-conditioned media. The BMSCs in experimental group 3 were loaded with FGF (3 ng/mL) and PDLF-conditioned media. The media was changed every 2 days. The cells of the control and experimental groups were cultured for 1, 11 and 14 days. The effects of the FGF and PDLF-conditioned media on fibroblast-related gene expression from the bone marrow stromal cells were examined by reverse transcription-polymerase chain reaction. Intensity of each band of the genes expressed was evaluated. The addition of FGF and PDLF-conditioned media enhanced the differentiation of fibroblast like cells from bone marrow stromal cell. The experimental group-treated FGF and PDLFconditioned media showed the strong expression of the fibroblast cell-specific marker: UNCL-, S100A2- and S100A4-mRNA at 14 days. Strong nestin mRNA expression was observed in the control group. This study suggests that FGF and PDLF-conditioned medium can enhance fibroblast-related gene expression in BMSCs in vitro.