• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2002.11a
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• pp.14-40
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• 2002

15-Deoxy-${\Delta}^{12, 14}$-prostaglandin $J_2$ (15-deoxy-$PGJ_2$), a naturally occurring ligand activates the peroxisome proliferator-activated $receptor-{\gamma}(PPAR-{\gamma}$). Activation of $PPAR-{\gamma}$ has been found to induce cell differentiation such as adipose cell and macrophage. Here it was investigated whether 15-deoxy-$PGJ_2$ has neuronal cell differentiation and possible underlying molecular mechanisms. Dopaminergic differentiating PC 12 cells treated with 15-deoxy-$PGJ_2$ (0.2 to 1.6 ${\mu}M$) alone showed measurable neurite extension and expression of neurofilament, markers of cell differentiation. However much greater extent of neurite extension and expression of neurofilament was observed in the presence of NGF (50 ng/ml). In parallel with its increasing effect on the neurite extension and expression of neurofilament, 15-deoxy-$PGJ_2$ enhanced NGF-induced p38 MAP kinase expression and its phosphorylation in addition to the activation of transcription factor AP-1 in a dose dependent manner. Moreover, pretreatment of SD 203580, a specific inhibitor of p38 MAP kinase inhibited the promoting effect of 15-deoxy-$PGJ_2$(0.8 ${\mu}M$) on NGF-induced neurite extension. This inhibition correlated well with the ability of SB203580 to inhibit the enhancing effect of 15-deoxy-$PGJ_2$ on the expression of p38 MAP kinase and activation of AP-1, The promoting ability of 15-deoxy-$PGJ_2$ did not occur through $PPAR-{\gamma}$, as synthetic PPAR-${\gamma}$ agonist andantagonist did not change the neurite promoting effect of 15-deoxy-PGJ$_2$. In addition, contrast to other cells (embryonic midbrain and SK-N-MC cells), $PPAR-{\gamma}$ was not expressed in PC-12 cells. Other structure related prostaglandins, PGD$_2$ and $PGE_2$ acting via a cell surface G-protein-coupled receptor (GPCR) did not increase basal or NGF-induced neurite extension. Moreover, GPCR (EP and DP receptor) antagonists did not alter the promoting effect of f 5-deoxy-$PGJ_2$ on neurite extension and activation of p38 MAP kinase, suggesting that the promoting effect of 15-deoxy-$PGJ_2$ may not be mediated GPCR. These data demonstrate that activation of p38 MAP kinase in conjunction with AP-1 single pathway may be important in the promoting activity of 15-deoxy-$PGJ_2$ cells.

• The Journal of Internal Korean Medicine
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• v.25 no.2
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• pp.202-213
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• 2004

Object : Objective: This study was conducted to investigate the anti-cancer effects of Mylabris phalerata (반모) in some kinds of cancer cells. Materials and Methods: Some kinds of cancer cells lines were treated. We used nine kinds of cancer cell lines, such as stomach cancer cells (Kato), lung cancer cells (Calu-1, NCI-H 1395), urinary bladder cancer cells (HS789T), bone cancer cells (Saos-2), brain cancer cells (SK-N-MC), liver cancer cells (Hep-G2), skin cancer cells (Mo-1) and prostate cancer cells (PC-3) with the water decoction of Mylabris phalerata. The histological changes of all cell lines in the media (RPMI-1640) containing the decoction of Mylabris phalerata were observed and we examined cell death assay by trypan blue exclusion testing was examined. Finally, the change of mitochondrial membrane potential was measurd and the inhibitory effect of Mylabris phalerata on cell increase was examined by analyzing the cell cycle. Results: In histologic change all cancer cell lines showed withdrawn and floating appearance that is typical in cellular impairment. Most of the cell lines showed over 50% death rate after 24 hours in trypan blue exclusion tests. Especially the stomach, urinary bladder. brain and liver cell lines showed over 30% death rate after 12 hours. All cell lines treated with Mylabris phalerata were less stained than the control group and the mitochondrial membrane potential in the Mylabris phalerata treated cell lines was markedly lower than that in the control group. The measurement of DNA quantity in all cell lines showed the disappearance of the peak and the thickened left axis, which suggests that all cellular DNA degraded. Conclusion: Mylabris phalerata had cytotoxicity on various kinds of cancer cell lines and the mechanism of that was the impairment of mitochondria by the breakdown of the mitochondrial cell membrane. We propose that this is in part attributable to the destruction of DNA in cancer cells.

• The Journal of Korean Medicine
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• v.27 no.2 s.66
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• pp.122-133
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• 2006

Objectives : The amyloid $\beta$-protein ($A\beta$) is the principal component of the senile plaques characteristic of Alzheimer's disease (AD) and elicits a toxic effect on neurons in vitro and in vivo. Many environmental factors including antioxidants and proteoglycans modify $A{\beta}toxicity$. In this study, we have investigated the protective effects of water- and organic solvent-extracts of Hemerocallis fulva root fractions pre-extracted with methanol on $A\beta$-induced oxidative cell death in cultured rat pheochromocytoma (PC12) cells. Methods : For this study, we used MTT reduction assay for detection of protective effects of water- and organic solvent-extracts of Hemerocallis fulva root fractions pre-extracted with methanol on $A{\beta}_{25-35}$-induced cytotoxicity to PC12 cells. We also used cell-based $\beta$-secretase assay system to investigate the inhibitory effect of water- and organic solvent-extracts of Hemerocallis fulva root on $\beta$-secretase activity. Results : We previously reported that methanol extracts of Hemerocallis fulva root strongly attenuated cytotoxicity induced by the three $A\beta$ fragments ($A{\beta}_{25-35},\;A{\beta}_{1-42}\;A{\beta}_{1-43}$) to both SK-N-MC and PC12 cells. In the present study, we found that butanol-, ethylacetate-, chloroform-, and water-extracts of Hemerocallis fulva root fractions pre-extracted with methanol had strong protective effects against $A{\beta}_{25-35}$-induced cytotoxicity to PC12 cells and inhibitory potency to $\beta$-secretase activity. Conclusion : These results suggest that butanol-, ethylacetate-, chloroform-, and water-extracts of Hemerocallis fulva root fractions pre-extracted with methanol may contain the protective component(s) against $A\beta$-induced cell death in PC12 cells as well as inhibitory component(s) to $\beta$-secretase activity.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.8
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• pp.3435-3442
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• 2015

Objective : To provide background information for strengthening cervical cancer prevention in the Pacific by mapping current human papillomavirus (HPV) vaccination and cervical cancer screening practices, as well as intent and barriers to the introduction and maintenance of national HPV vaccination programmes in the region. Materials and Methods: A cross-sectional questionnaire-based survey among ministry of health officials from 21 Pacific Island countries and territories (n=21). Results: Cervical cancer prevention was rated as highly important, but implementation of prevention programs were insufficient, with only two of 21 countries and territories having achieved coverage of cervical cancer screening above 40%. Ten of 21 countries and territories had included HPV vaccination in their immunization schedule, but only two countries reported coverage of HPV vaccination above 60% among the targeted population. Key barriers to the introduction and continuation of HPV vaccination were reported to be: (i) Lack of sustainable financing for HPV vaccine programs; (ii) Lack of visible government endorsement; (iii) Critical public perception of the value and safety of the HPV vaccine; and (iv) Lack of clear guidelines and policies for HPV vaccination. Conclusion: Current practices to prevent cervical cancer in the Pacific Region do not match the high burden of disease from cervical cancer. A regional approach, including reducing vaccine prices by bulk purchase of vaccine, technical support for implementation of prevention programs, operational research and advocacy could strengthen political momentum for cervical cancer prevention and avoid risking the lives of many women in the Pacific.

• Proceedings of the Korean Society of Toxicology Conference
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• 2002.11b
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• pp.14-40
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• 2002

15-Deoxy- Δ$\^$12,14/-prostaglandin J$_2$ (15-deoxy-PGJ$_2$), a naturally occurring ligand activates the peroxisome proliferator-activated receptor-${\gamma}$ (PPAR-${\gamma}$). Activation of PPAR-y has been found to induce cell differentiation such as adipose cell and macrophage. Here it was investigated whether 15-deoxy-PGJ$_2$ has neuronal cell differentiation and possible underlying molecular mechanisms. Dopaminergic differentiating PC 12 cells treated with 15-deoxy-PGJ$_2$ (0.2 to 1.6 ${\mu}$M) alone showed measurable neurite extension and expression of neurofilament, markers of cell differentiation. However much greater extent of neurite extension and expression of neurofilament was observed in the presence of NGF (50 ng/$m\ell$). In parallel with its increasing effect on the neurite extension and expression of neurofilament, 15-deoxy-PGJ$_2$ enhanced NGF-induced p38 MAP kinase expression and its phosphorylation in addition to the activation of transcription factor AP-1 in a dose dependent manner. Moreover, pretreatment of SD 203580, a specific inhibitor of p38 MAP kinase inhibited the promoting effect of 15-deoxy-PGJ$_2$ (0.8 ${\mu}$M) on NGF-induced neurite extension. This inhibition correlated well with the ability of SB203580 to inhibit the enhancing effect of 15-deoxy-PGJ$_2$ on the expression of p38 MAP kinase and activation of AP-1. The promoting ability of 15-deoxy-PGJ$_2$ did not occur through PPAR-${\gamma}$, as synthetic PPAR-${\gamma}$ agonist and antagonist did not change the neurite promoting effect of 15-deoxy-PGJ$_2$. In addition, contrast to other cells (embryonic midbrain and SK-N-MC cells), PPAR-${\gamma}$ was not expressed in PC-12 cells. Other structure related prostaglandins, PGD$_2$ and PGE$_2$ acting via a cell surface G-protein-coupled receptor (GPCR) did not increase basal or NGF-induced neurite extension. Moreover, GPCR (EP and DP receptor) antagonists did not alter the promoting effect of 15-deoxy-PGJ$_2$ on neurite extension and activation of p38 MAP kinase, suggesting that the promoting effect of 15-deoxy-PGJ$_2$ may not be mediated GPCR. These data demonstrate that activation of p38 MAP kinase in conjunction with AP-1 signal pathway may be important in the promoting activity of 15-deoxy-PGJ$_2$ on the differentiation of PC12 cells.