• Journal of Food Hygiene and Safety
• /
• v.28 no.3
• /
• pp.202-206
• /
• 2013

High-grade mucoepidermoid carcinomas (MECs) have difficulty in cure and 5-year survival rate is quiet low. Therefore, we need new therapeutic agents and molecular targets. Betulinic acid (BA) is one of the materials which is easily found in the world and shows tumor-suppress effects in various tumor types. In addition, many kinds of normal tissues have a resistance to BA treatment. In this study, we investigated the anti-proliferative activity of BA and its molecular targets in MC-3 human MEC cells using western blot analysis and DAPI staining. BA inhibited cell viability and induced apoptosis in MC-3 cells. It affected Specificity protein 1 (Sp1) and its downstream molecule, survivin whereas it did not affect myeloid cell leukemia-1 (Mcl-1). Therefore, we suggest that BA can be a potential anti-cancer drug candidate regulating Sp 1 and survivin to exert apoptotic cell death.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.18 no.4
• /
• pp.1120-1128
• /
• 2004

Zinc ion has both essential and toxic effects on mammalian cells. The results demonstrated that the ability of zinc to act as an inducer of apoptosis in C6 glial cells. Incubation with 0.2 mM ZnCl₂ caused cell death that was characterized as apoptosis by internucleosomal DNA fragmentation, formation of apoptotic bodies, nuclear fragmentation and breakdown of the mitochondrial membrane potential. ZnCl₂-induced apoptosis of C6 glial cells was prevented by the addition of Sibjeondaebo-Tang and antioxidants including reduced glutathione, N-acetyl-L-cysteine. We further confirmed that ZnCl₂ decreased the intracellular levels of GSH as well as generation of H₂O₂ in C6 glial cells. In 2D-electrophoresis, computer-assisted comparative analysis of the respective silver stained spot patterns revealed 3 groups with strongly decreased intensity by ZnCl₂. Whereas, 3 groups with increasing intensity were recovered by Sibjeondaebo-Tang. These results suggest that Sibjeondaebo-Tang may function as an antioxidant against free radicals and be applicable to the treatment of brain cells against oxidative stress.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.18 no.5
• /
• pp.1418-1425
• /
• 2004

The water extract of Chongmyung-tang has been traditionally used for treatment of memory-disorder in oriental medicine. This study was designed to investigate the protective mechanisms of Chongmyung-tang on β-amyloid or H₂O₂-induced cytotoxicity in Neuro 2A cells. The water extract of Chongmyung-tang significantly reduced both β-amyloid or H₂O₂-induced cell death and apoptotic characteristics through reduction of intracellular peroxide generation. Also, it inhibited the mitochondrial dysfunction including the disruption of mitochondria membrane permeability transition(MPT) and the modulation in expression of Bcl-2 family proteins in H₂O₂-treated H9c2 cells. Furthermore, pretreatment of quercetin inhibited the activation of caspase-3, in turn, degradation of ICAD/DFF45 were completely abolished in H₂O₂-treated cells. Taken together, that data suggest that the protective effects of the water extract of Chongmyung-tang against β-amyloid induced oxidative injuries may be achieved through modulation of mitochondrial dysfunction.

• Toxicological Research
• /
• v.21 no.1
• /
• pp.77-85
• /
• 2005

Cadmium is an environmental pollutant exposed from contaminated foods or cigarette smoking and known to cause oxidative damage in organs. We investigated the cadmium-induced apoptosis and cell arrest in human breast cancer cells, MCF-7 cells and MDA-MB-231 cells. Obvious apoptotic cell death was shown in CdCl₂ 100 μM treatment for 12 hr, which were determined by DAPI staining and flow cytometric analysis. In cell cycle analysis, MCF-7 cells and MDA-MB-231 cells were arrested in S phase and G2/M phase respectively. These could be explained by the induction of cell cycle inhibitory protein, p21/sup Waf1/Cip1/ and p27/sup Kip1/, expression and reduction of cyclin/Cdk complexes in both cell lines. The decreased expression of cyclin A and Cdk2 in MCF-7 cells and cyclin B1 and Cdc2 in MDA-MB-231 cells were consistent with the flow cytometric observation. p-ERK expression was increased dose-dependent manner in both cell lines. It suggests that ERK MAPK pathway are involved in cadmium-induced cell cycle arrest and apoptosis. Moreover, cotreatment of zinc (100 μM, 12 hr) recovered the cadmium-induced cell arrest in both cells, which shows cadmium-induced oxidative stress mediates apoptosis and cell cycle arrest in human breast cancer cells.

• Natural Product Sciences
• /
• v.10 no.3
• /
• pp.124-128
• /
• 2004

Previously, $(1R,9S)-{\beta}-Hydrastine$ hydrochloride has been found to lower dopamine content in PC12 cells (Kim et al., 20001). In this study, the effects of $(1R,9S)-{\beta}-Hydrastine$ hydrochloride on L-DOPA-induced cytotoxicity in PC12 cells were investigated. Treatment with $(1R,9S)-{\beta}-Hydrastine$ hydrochloride at concentrations higher than $500\;{\mu}M$ caused cytotoxicity in PC12 cells. In addition, $(1R,9S)-{\beta}-Hydrastine$ hydrochloride at non-cytotoxic or cytotoxic concentrations significantly enhanced L-DOPA-induced cytotoxicity (L-DOPA concentration, $50\;{\mu}M$). Treatment of PC12 cells with $750\;{\mu}M$ $-1R,9S)-{\beta}-Hydrastine$ hydrochloride and $50\;{\mu}M$ L-DOPA, alone or in combination, also induced cell death via a mechanism which exhibited morphological and biochemical characteristics of apoptosis, including chromatin condensation and membrane blebbing. Exposure of PC12 cells to $(1R,9S)-{\beta}-Hydrastine$ hydrochloride, L-DOPA and $(1R,9S)-{\beta}-Hydrastine$ hydrochloride plus L-DOPA for 48 h resulted in a marked increase in the cell loss and percentage of apoptotic cells compared with exposure for 24 h. These data indicate that $(1R,9S)-{\beta}-Hydrastine$hydrochloride at higher concentration ranges aggravates L-DOPA-induced neurotoxicity cytotoxicity in PC12 cells. Therefore, it is proposed that the long-term L-DOPA therapeutic patients with $(1R,9S)-{\beta}-Hydrastine$ hydrochloride could be checked for the adverse symptoms.

• Biomolecules & Therapeutics
• /
• v.28 no.2
• /
• pp.195-201
• /
• 2020

Prostate cancer is one of the most common cancers in men. Choline PET or PET/CT has been used to visualize prostate cancer, and high levels of choline accumulation have been observed in tumors. However, the uptake system for choline and the functional expression of choline transporters in prostate cancer are not completely understood. In this study, the molecular and functional aspects of choline uptake were investigated in the LNCaP prostate cancer cell line along with the correlations between choline uptake and cell viability in drug-treated cells. Choline transporter-like protein 1 (CTL1) and CTL2 mRNA were highly expressed in LNCaP cells. CTL1 and CTL2 were located in the plasma membrane and mitochondria, respectively. [³H]Choline uptake was mediated by a single Na⁺-independent, intermediate-affinity transport system in the LNCaP cells. The anticancer drugs, flutamide and bicalutamide, inhibited cell viability and [³H]choline uptake in a concentration-dependent manner. The correlations between the effects of these drugs on cell viability and [³H]choline uptake were significant. Caspase-3/7 activity was significantly increased by both flutamide and bicalutamide. Furthermore, these drugs decreased CTL1 expression in the prostate cancer cell line. These results suggest that CTL1 is functionally expressed in prostate cancer cells and are also involved in abnormal proliferation. Identification of this CTL1-mediated choline transport system in prostate cancer cells provides a potential new therapeutic target for the treatment of this disease.

• Journal of Plant Biotechnology
• /
• v.43 no.4
• /
• pp.432-437
• /
• 2016

Interleukin-11 (IL-11) is a cytokine that plays a key regulatory role in the immune system. Recombinant human IL-11 (rhIL-11) exerts a preventative effect against apoptotic cell death and inhibits preadipocyte differentiation. IL-11 also is used to stimulate the bone marrow to produce platelets in order to prevent low platelets that may be caused by chemotherapy. Unfortunately, the high production cost of IL-11 associated. In this study, we investigated the feasibility of transgenic plants for the cost-effective production of rhIL-11. Production of rhIL-11 proteins in whole-plant expression system will be more economical when compared to the current E. coli based expression system. The human rhIL-11 gene was codon optimized to maximize plant host system expression. IL-11 expression vector under the control of a constitutive cauliflower mosaic virus 35S (CaMV 35S) promoter was introduced into tobacco by Agrobacterium-mediated transformation. The 5'-leader sequence (called ${\Omega}$) of tobacco mosaic virus (TMV) as a translational enhancer was added to construct. Transgenic tobacco plants expressing various levels of rhIL-11 protein were generated. Western blotting of the stably transformed lines demonstrated accumulation of the appropriately sized rhIL-11 protein in leaves. This research demonstrated the efficacy of using tobacco as an expression system for the production of rhIL-11.

• Korean Journal of Medicinal Crop Science
• /
• v.14 no.2
• /
• pp.70-76
• /
• 2006

Paeoniae radix has been widely used for its anti-allergic, anti-inflammatory and analgesic effects, and demonstrated to have anticonvulsant, memory enhancing and anxiolytic activities. The present study was performed to examine the protective effect of methanol extract of Paeoniae radix (PR) from Paeoniae Japonica Miyabe et Takeda (Paeoniaceae) on hydrogen peroxide $(H_2O_2)-induced$ neurotoxicity using cultured rat cerebral cortical neuron. $H_2O_2$ produced a concentration-dependent reduction of neuronal viability, PR, over a concentration range of 10 to $100\;{\mu}g/ml$ showed concentration-dependent decrease of the $H_2O_2$$(100\;{\mu}M)-induced$ neuronal cell death, as assessed by a 3-[4,5-dimethylthiazol-2-yl]-2,5-di-phenyl-tetrazolium bromide assay and the number of apoptotic nuclei, evidenced by Hoechst 33342 staining. PR $(100\;{\mu}g/ml$ inhibited $100\;{\mu}M$ $H_2O_2-induced$ elevation of the cytosolic $Ca^{2+}$ concentration $([Ca^{2+}]_c)$, which was measured by a fluorescent dye, flue-4 AM. PR $(50\;{\mu}g/ml$ inhibited glutamate release into medium induced by $100\;{\mu}M$ $H_2O_2$, which was measured by HPLC, and generation of reactive oxygen species (ROS). These results suggest that PR may mitigate the $H_2O_2-induced$ neurotoxiciy by interfering with the increase of $[Ca^{2+}]_c$, and then inhibiting glutamate release and generation of ROS in cultured neurons.

• Korean Journal of Pharmacognosy
• /
• v.32 no.4 s.127
• /
• pp.274-279
• /
• 2001

Ailanthus altissima belonging to the family Simaroubaceae has been used to settle an upset stomach, to combat a fever, and as an insecticide. Apoptosis is an active process, which is a critical feature of the regulated development of multicellular organisms. We investigated whether the extract of A. altissima induced apoptotic cell death in Jurkat T-acute lymphoblastic leukemia (ALL) cells. Upon treatments with the extract, the dose-dependent inhibitions of cell viability were observed. It also caused apoptosis as measured by cell morphology and DNA fragmentation. The capability of the extract to induce apoptosis was associated with proteolytic cleavage of specific target protein such as poly(ADP-ribose)polymerase (PARP) protein, suggesting the possible involvement of the activations of caspases. Further study showed that Bcl-2 protein levels were not changed in all treated groups compared to control group. These results suggest that A. altissima induces Bcl- 2-independent apoptosis in Jurkat T cells.

• Korean Journal of Pharmacognosy
• /
• v.40 no.4
• /
• pp.351-356
• /
• 2009

Many isoquinoline alkaloids including berberine lower dopamine content by reducing tyrosine hydroxylase (TH) activity and aggravate L-DOPA-induced cytotoxicity in PC12 cells. In this study, the effects of berberine on 6-hydroxydopamine (6-OHDA)-induced cytotoxicity in PC12 cells and on unilateral 6-OHDA-lesioned rat models were investigated. Berberine at 10-30 ${\mu}M$ did not affect cell viability in PC12 cells. However, berberine at concentrations higher than $50{\mu}M$ caused cytotoxicity at 24 h. Berberine (10-50 ${\mu}M$) also enhanced 6-OHDA (10-50 ${\mu}M$)-induced cytotoxicity at 24 h compared to 6-OHDA alone with an apoptotic process. In addition, treatment with berberine (5 and 30 mg/kg, i.p.) for three weeks showed a dopaminergic cell loss in substantia nigra of 6-OHDA-lesioned rats: 30 mg/kg berberine was more intensive cytotoxic. The levels of dopamine were also decreased by berberine (5 and 30 mg/kg) in the ipsilateral substantia nigra of 6-OHDA-lesioned rats. These results suggest that berberine aggravated 6-OHDA-induced cytotoxicity in PC12 cells and treatment with berberine (5 and 30 mg/kg) in 6-OHDA-lesioned rats also enhanced the degeneration of dopaminergic cell death and the decrease in dopamine levels in substantia nigra. Therefore, the long-term L-DOPA therapeutic patients with isoquinoline compounds including berberine may need to be checked for the adverse symptoms.