• Food preservation and processing industry
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• v.6 no.2
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• pp.11-13
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• 2007

This study relates to low and medium molecular weight isoflavone-${\beta}$-D-glucan produced by submerged liquid culture of Agaricus blazei, a method of producing the isoflavone-B-D-glucan using autolysis enzyme of Agaricus blazei mycelia, and use of the isoflavone-B-D-glucan for anti-cancer and immunoenhancing effect. In acordance with one aspect of the present study, it deals with a method of producing isoflavone-${\beta}$-D-glucan, which comprises the followings; 1) culturing and separating mushroom mycelia, 2) producing low-medium molecular weight isoflavone-${\beta}$-D-glucan from high molecular weight one. The cytotoxicity on human cnacer cell line (Caco-2, MCF-7), the expression of Cyclin D, Bcl-2, Bax protein, p21 protein, p53 protein in MCF-7 cells assessed by SDS-PAGE and immunoblotting, and other immuno related factor such as TNF-a and IL-1B activities were examined. Structural identification of isoflavone-${\beta}$-D-glucan which shoed cytotoxicity against cancer cell and immunoenhancing effects was carried by separation with DEAE-cellulose column chromatography, TLC, HPLC, IR, NMR, Clinical test for the cancer patients (n=119) for 6 month was carried out, and immunoenhancing factors(NK cell number, ratio of T4/T8) were checked. We concluded the identified isoflavone-${\beta}$-D-glucan has immuno enhancing effects and could be useful for cancer chemoprevention.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.5
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• pp.421-426
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• 2015

The increased potential for vascular smooth muscle cell (VSMC) growth is a key abnormality in the development of atherosclerosis and post-angioplasty restenosis. Abnormally high activity of platelet-derived growth factor (PDGF) is believed to play a central role in the etiology of these pathophysiological situations. Here, we investigated the anti-proliferative effects and possible mechanism(s) of murrayafoline A, a carbazole alkaloid isolated from Glycosmis stenocarpa Guillamin (Rutaceae), on PDGF-BB-stimulated VSMCs. Murrayafoline A inhibited the PDGF-BB-stimulated proliferation of VSMCs in a concentration-dependent manner, as measured using a non-radioactive colorimetric WST-1 assay and direct cell counting. Furthermore, murrayafoline A suppressed the PDGF-BB-stimulated progression through $G_0/G_1$ to S phase of the cell cycle, as measured by [$^3H$]-thymidine incorporation assay and cell cycle progression analysis. This anti-proliferative action of murrayafoline A, arresting cell cycle progression at $G_0/G_1$ phase in PDGF-BB-stimulated VSMCs, was mediated via down-regulation of the expression of cyclin D1, cyclin E, cyclin-dependent kinase (CDK)2, CDK4, and proliferating cell nuclear antigen (PCNA), and the phosphorylation of retinoblastoma protein (pRb). These results indicate that murrayafoline A may be useful in preventing the progression of vascular complications such as restenosis after percutaneous transluminal coronary angioplasty and atherosclerosis.

• Proceedings of the Korean Society of Postharvest Science and Technology of Agricultural Products Conference
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• 2007.11a
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• pp.27-31
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• 2007

This study relates to low and medium molecular weight isoflavone-${\beta}$-D-glucan produced by submerged liquid culture of Agaricus blazei, a method of producing the isoflavone-B-D-glucan using autolysis enzyme of Agaricus blazei mycelia, and use of the isoflavone-B-D-glucan for anti-cancer and immunoenhancing effect. In acordance with one aspect of the present study, it deals with a method of producing isoflavone-${\beta}$-D-glucan, which comprises the followings; 1) culturing and separating mushroom mycelia, 2) producing low-medium molecular weight isoflavone-${\beta}$-D-glucan from high molecular weight one. The cytotoxicity on human cnacer cell line (Caco-2, MCF-7), the expression of Cyclin D, Bcl-2, Bax protein, p21 protein, p53 protein in MCF-7 cells assessed by SDS-PAGE and immunoblotting, and other immuno related factors such as TNF-${\alpha}$ and IL-1B activities were examined. Structural identification of isoflavone-${\beta}$-D-glucan which showed cytotoxicity against cancer cell and immunoenhancing effects was carried by separation with DEAE-cellulose column chromatography, TLC, HPLC, IR, NMR. Clinical test for the cancer patients (n=119) for 6 month was carried out, and immunoenhancing factors (NK. cell number, ratio of T4/T8) were checked. We concluded the identified isoflavone-${\beta}$-D-glucan has immuno enhancing effects and could be useful for cancer chemoprevention.

• Toxicological Research
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• v.31 no.4
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• pp.331-337
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• 2015

Synthetic pyrethroids (SPs) are the most common pesticides which are recently used for indoor pest control. The widespread use of SPs has resulted in the increased exposure to wild animals and humans. Recently, some SPs are suspected as endocrine disrupting chemicals (EDCs) and have been assessed for their potential estrogenicity by adopting various analyzing assays. In this study, we examined the estrogenic effects of lambda-cyhalothrin (LC) and cypermethrin (CP), the most commonly used pesticides in Korea, using BG-1 ovarian cancer cells expressing estrogen receptors (ERs). To evaluate the estrogenic activities of two SPs, LC and CP, we employed MTT assay and reverse-transcription polymerase chain reaction (RT-PCR) in LC or CP treated BG-1 ovarian cancer cells. In MTT assay, LC ($10^{-6}M$) and CP ($10^{-5}M$) significantly induced the growth of BG-1 cancer cells. LC or CP-induced cell growth was antagonized by addition of ICI 182,720 ($10^{-8}M$), an ER antagonist, suggesting that this effect appears to be mediated by an ER-dependent manner. Moreover, RT-PCR results showed that transcriptional level of cyclin D1, a cell cycle-regulating gene, was significantly up-regulated by LC and CP, while these effects were reversed by co-treatment of ICI 182,780. However, p21, a cyclin D-ckd-4 inhibitor gene, was not altered by LC or CP. Moreover, $ER{\alpha}$ expression was not significantly changed by LC and CP, while down-regulated by E2. Finally, in xenografted mouse model transplanted with human BG-1 ovarian cancer cells, E2 significantly increased the tumor volume compare to a negative control, but LC did not. Taken together, these results suggest that LC and CP may possess estrogenic potentials by stimulating the growth of BG-1 ovarian cancer cells via partially ER signaling pathway associated with cell cycle as did E2, but this estrogenic effect was not found in in vivo mouse model.

• The Korean Journal of Physiology and Pharmacology
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• v.16 no.5
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• pp.321-326
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• 2012

Resveratrol, a natural compound, has been shown to possess anti-cancer, anti-aging, anti-inflammatory, anti-microbial, and neuroprotective activities. In this study, we examined the antiproliferative and cytotoxicity properties of resveratrol in Rat B103 neuroblastoma cells; although it's molecular mechanisms for the biological effects are not fully defined. Here, we examined the cellular cytotoxicity of resveratrol by cell viability assay, antiproliferation by BrdU assay, DNA fragmentation by DNA ladder assay, activation of caspases and Bcl-2 family proteins were detected by western blot analyses. The results of our investigation suggest that resveratrol increased cellular cytotoxicity of Rat B103 neuroblastoma cells in a dose-and time-dependent manner with $IC_{50}$ of 17.86 ${\mu}M$ at 48 h. On the other hand, incubation of neuroblastoma cells with resveratrol resulted in S-phase cell cycle arrests which dose-dependently and significantly reduced BrdU positive cells through the downregulation of cyclin D1 protein. In addition, resveratrol dose-dependently and significantly downregulated the expression of anti-apoptotic protein includes Bcl-2, Bcl-xL and Mcl-1 and also activates cleavage caspase-9 and-3 via the downregulation of procaspase-9 and -3 in a dose-dependent manner which indicates that involvement of intrinsic mitochondria-mediated apoptotic pathway. In conclusion, resveratrol increases cellular cytotoxicity and inhibits the proliferation of B103 neuroblastoma cells by inducing mitochondria-mediated intrinsic caspase dependent pathway which suggests this natural compound could be used as therapeutic purposes for neuroblastoma malignancies.

• The Journal of Korean Obstetrics and Gynecology
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• v.21 no.2
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• pp.38-48
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• 2008

Purpose: This study was conducted to investigate the effects of Hominis Placenta (紫河車) on the growth of human uterine myoma cells and cell apoptosis. Methods: Human uterine leiomyoma cells were cultured and treated with Hominis Placenta extract for 48 hours. Cell proliferation and activity was analyzed by MTT assay. We analyzed the cell cycle of human uterine myoma cells treated Hominis Placenta extract by FACS. Expression of proteins related to cell apoptosis (Bax, Bcl-2), cyclin-D1 and VEGF were evaluated by Western blotting method. Results: The human uterine myoma cells treated by Hominis Placenta extract didn't proliferate below the concentration of $10mg/m{\ell}$. And there was no remarkable difference on cell cycle analysis below the concentration of $10mg/m{\ell}$. The expression of Bax was decreased and the expression of Bcl-2 was increased after the treatment of Hominis Placenta extract. But the expressions of cyclin-D1 and VEGF were increased after the treatment of Hominis Placenta extract. Conclusion: This study suggests that Hominis Placenta induce uterine myoma cell apoptosis and have effect on the myoma cell proliferation in the concentraion below $10mg/m{\ell}$.

• The Journal of Korean Obstetrics and Gynecology
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• v.21 no.2
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• pp.17-26
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• 2008

Purpose: This study was conducted to investigate the effects of Cervi Pontotrichum Cornu extract solution on the cell cycle regulation and apoptosis in human leiomyoma cell. Methods: The leiomyoma cell of patients was used in the study, and we administered the extract solution of Cervi Pontotrichum Cornu concentration at 1, $10mg/m{\ell}$ to the leiomyoma cell for 48 hours. We used flow cytometry and western blotting to confirm cell cycle and apoptosis. Results: In flow cytometry, G1 phase of the $1mg/m{\ell}$ group prolonged. But G1 phase of $10mg/m{\ell}$ group was shortened and S phase was increased. Cyclin D1 expression increased in higher concentration group. And Bax expression that regulates cell apoptosis increased in $1mg/m{\ell}$ and $10mg/m{\ell}$ group than control group. Bcl-2 expression decreased in 1, $10mg/m{\ell}$ groups than control group. VEGF expression rised in higher Cervi Pontotrichum Cornu concentration group. Conclusion: This study means that Cervi Pontotrichum Cornu could induce the apoptosis of leiomyoma cell by increasing Bax and decreasing Bcl-2 expression. But Cervi Pontotrichum Cornu could increase Cyclin D1 and VEGF expression, so more detailed studies would be needed.

• Biomolecules & Therapeutics
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• v.20 no.3
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• pp.313-319
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• 2012

In recent years, inhibition of HDACs has emerged as a potential strategy to reverse aberrant epigenetic changes associated with cancer, and several classes of HDAC inhibitors have been found to have potent and specific anticancer activities in preclinical studies. But their precise mechanism of action has not been elucidated. In this study, a novel synthetic inhibitor of HDAC, 3-(4-dimethylamino phenyl)-N-hydroxy-2-propenamide [IN-2001] was examined for its antitumor activity and the underlying molecular mechanisms of any such activity on human breast cancer cell lines. IN-2001 effectively inhibited cellular HDAC activity ($IC_{50}$ = 0.585 nM) inMDA-MB-231 human breast cancer cells. IN-2001 caused a significant dose-dependent inhibition of cell proliferation in estrogen receptor (ER) negative MDA-MB-231human breast cancer cells. Cell cycle analysis revealed that the growth inhibitory effects of IN-2001 might be attributed to cell cycle arrest at $G_0/G_1$ and/or $G_2$/Mphase and subsequent apoptosis in human breast cancer cells. These events are accompanied by modulating several cell cycle and apoptosis regulatory genes such as CDK inhibitors $p21^{WAF1}$ and $p27^{KIP1}$ cyclin D1, and other tumor suppressor genes such as cyclin D2. Collectively, IN-2001 inhibited cell proliferation and induced apoptosis in human breast cancer cells and these findings may provide new therapeutic approaches, combination of antiestrogen together with a HDAC inhibitor, in the hormonal therapy-resistant ER-negative breast cancers. In summary, our data suggest that this histone deacetylase inhibitor, IN-2001, is a novel promising therapeutic agent with potent antitumor effects against human breast cancers.

• Journal of Microbiology and Biotechnology
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• v.33 no.3
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• pp.398-409
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• 2023

LncRNAs play crucial roles in the progression of colon adenocarcinoma (COAD), but the role of LINC01232 in COAD has not received much attention. The present study was designed to explore the related mechanisms of LINC01232 in the progression of COAD. LINC01232, miR-181a-5p, p53, c-myc, Bcl-2, cyclin D1, p16, Bax, VEGF, E-cadherin, vimentin, N-cadherin and SDAD1 expressions were determined by western blot and qRT-PCR. CCK-8, tubule formation, and Transwell assays were employed to detect proliferation, angiogenesis, and migration/invasion of COAD cells, respectively. The relationship between LINC01232 and miR-181a-5p was predicted by LncBase Predicted v.2, and then verified through dual luciferase reporter gene assay. According to the results, LINC01232 was highly expressed in COAD cells and enhanced proliferation, angiogenesis, migration, and invasion of COAD cells. Downregulated LINC01232 promoted expression of p53 and p16, and inhibited c-myc, Bcl-2 and cyclin D1 expressions in COAD cells, while upregulation of LINC01232 generated the opposite effects. LINC01232 was negatively correlated with miR-181a-5p while downregulated miR181a-5p could reverse the effects of siLINC01232 on cell proliferation, angiogenesis, migration, and invasion. Similarly, miR-181a-5p mimic could also offset the effect of LINC01232 overexpression. SiLINC01232 increased the expressions of Bax and E-cadherin, and decreased the expressions of VEGF, vimentin, N-cadherin and SDAD1, which were partially attenuated by miR-181a-5p inhibitor. Collectively, LINC01232 enhances the proliferation, migration, invasion, and angiogenesis of COAD cells by decreasing miR-181a-5p expression.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.1
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• pp.204-208
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• 2007

Chaga mushroom extract is well known as immune modulator and anti-cancer agent. However, the molecular mechanism by which Chaga exerts cell cycle arrest and apoptosis of cancer cells is poorly understood. In this study, we demonstrated anti-proliferative effects of Chaga extract on murine melanoma B16 cells. Chaga extract dose-dependently inhibited cell growth along with the arrest of G0/G1 phase and the induction of apoptotic cell death. Treatment with Chaga extract resulted in a decrease of cyclin E, cyclin D1, cdk 2, cdk 4 expression levels. Furthermore, in vivo inoculation study of B16 melanoma cells into Balb/c mice Chaga extract markedly suppressed the metastatic growth of tumor cells (6 folds, p<0.05,). These results indicate that Chaga mushroom extract induces apoptosis of B16 melanoma cells through arrest of G0/G1 phase in cell cycle.