• The Journal of Korean Obstetrics and Gynecology
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• v.18 no.1
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• pp.181-191
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• 2005

Purpose : ${\beta}$-sitosterol is kind of phytosterols or plant which are structurally similar to cholesterol. This study was aimed to investigate the inhibitory effect of the ${\beta}$-sitosterol on the proliferation of human uterine leiomyoma cells and the expression of gene related the mechanism of cell apoptosis. Methods : We counted the number of death cells treated with indicated time of the ${\beta}$-sitosterol and investigated cell death rate by cell count assay. Furthermore, flow cytometry analysis and DNA fragmentation assay were used to dissect between necrosis and apoptosis. and then we observed the differential gene expression by western blot analysis. Results : 1) The inhibitory effect on the growth of uterine leiomyoma cell treated with the ${\beta}$-sitosterol $16{\mu}M$ was increased in a time dependent. 2) The result of flow cytometry analysis, subG1 phase arrest related cell apoptosis was investigated 16.97% in uterine leiomyoma cell treated with the ${\beta}$-sitosterol $16{\mu}M$ and showed the fashion of proportional time dependent. 3) The gene expression of p27, p21 related cell cycle was increased according to increasing time interval but cyclin E-CDK2 complex was decreased expression. 4) The character of apoptosis, DNA fragmentation was significantly observed on the time dependent. 5) The expression of pro-caspase 3 and PARP were decreased dependent on treatment with time dependent. Conclusion : This study showed that the ${\beta}$-sitosterol have the inhibitory effect on the proliferation of human uterine leiomyoma cell and the effect was related with apoptosis.

• Biomolecules & Therapeutics
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• v.30 no.2
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• pp.151-161
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• 2022

This study elucidates the anti-cancer potential of gallic acid (GA) as a promising therapeutic agent that exerts its effect by regulating the PI3K/Akt pathway. To prove our research rationale, we used diverse experimental methods such as cell viability assay, colony formation assay, tumor spheroid formation assay, cell cycle analysis, TUNEL assay, Western blot analysis, xenograft mouse model and histological analysis. Treatment with GA inhibited cell proliferation in dose-dependent manner as measured by cell viability assay at 48 h. GA and cisplatin (CDDP) also inhibited colony formation and tumor spheroid formation. In addition, GA and CDDP induced apoptosis, as determined by the distribution of early and late apoptotic cells and DNA fragmentation. Western blot analysis revealed that inhibition of the PI3K/Akt pathway induced upregulation of p53 (tumor suppressor protein), which in turn regulated cell cycle related proteins such as p21, p27, Cyclin D1 and E1, and intrinsic apoptotic proteins such as Bax, Bcl-2 and cleaved caspase-3. The anti-cancer effect of GA was further confirmed in an in vivo mouse model. Intraperitoneal injection with GA for 4 weeks in an A549-derived tumor xenograft model reduced the size of tumor mass. Injection of them downregulated the expression of proliferating cell nuclear antigen and p-Akt, but upregulated the expression of cleaved caspase-3 in tumor tissues. Taken together, these results indicated that GA hindered lung cancer progression by inducing cell cycle arrest and apoptosis, suggesting that GA would be a potential therapeutic agent against non-small cell lung cancer.

• Journal of Physiology & Pathology in Korean Medicine
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• v.38 no.1
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• pp.38-45
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• 2024

To compare and analyze the improvement effects of white ginseng extract, red ginseng extract, and black ginseng extract on cognitive dysfunction and memory impairment caused by scopolamine in rats. In the cognitive behavioral test, the tendency of the SCOP+B group to overcome the escape time delay induced by scopolamine administration was observed, unlike the SCOP group. The frequency on plat form was significantly increased in the group treated with ginseng extracts compared to the SCOP group. As a result of measuring the duration time on goal quadrant, the time spent in the quadrant was significantly increased in the SCOP+B group compared to the SCOP group. In the hippocampus, the SCOP-treated group significantly decreased the activity of AChE compared to the normal group, but the ginseng extract-treated groups significantly increased it compared to the SCOP group. After sacrificing the rats after the behavioral test, the expression of PSD95 protein in the excised brain was significantly decreased in the SCOP group compared to normal, but it was observed that the SCOP+R and SCOP+B groups were significantly increased compared to the SCOP group. CREB1 protein expression was significantly increased in the SCOP+R group, and the expression of Cdk5 was significantly increased in the SCOP+B group. Ginseng extracts significantly restored the memory damaged by scopolamine suggesting that red ginseng increased the expression of CREB1 and PSD95 proteins, and black ginseng increased the protein expression of Cdk5 and PSD95 to induce memory recovery.

• Journal of Life Science
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• v.24 no.2
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• pp.137-147
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• 2014

Cortex ulmi pumilae, the cortex of Ulmus davidiana var. japonica, has been used in traditional folk medicine for its anti-inflammatory effect. Although its various bioactivities such as anti-inflammatory, anti-microbial, and anti-cancer, have been reported, the anti-adipogenic activity of cortex ulmi pumilae remains unclarified. In the present study, we investigated the effect of cortex ulmi pumilae extract on adipocyte differentiation in 3T3-L1 preadipocytes. Treatment with cortex ulmi pumilae extract significantly reduced the formation of lipid droplets and triglyceride content in a dose-dependent manner; this is associated with an inhibition of the adipogenic transcription factors, CCAAT/enhancer binding protein ${\alpha}$ ($C/EBP{\alpha}$), $C/EBP{\beta}$, and peroxisome proliferator-activated receptor ${\gamma}$ ($PPAR{\gamma}$). In addition, cortex ulmi pumilae extract treatment during the early stage of adipogenesis showed more efficient anti-adipogenic activity than treatment during other stages of adipogenesis. Cortex ulmi pumilae extract also inhibited cell proliferation and induced G1 arrest of 3T3-L1 cells in the early stage of adipogenesis. This was associated with upregulated expression of Cdk inhibitor p21 and downregulated expression of cyclin E and phospho-Rb, indicating that cortex ulmi pumilae extract blocks mitotic clonal expansion by cell cycle regulation. Taken together, these results suggest that cortex ulmi pumilae extract possesses anti-adipogenic activity through the inhibition of adipocyte differentiation by blocking mitotic clonal expansion.

• Journal of Life Science
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• v.21 no.10
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• pp.1494-1499
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• 2011

${\beta}$-lapachone, a quinone of lapachol extracted from the bark of the lapacho tree, has been found to induce apoptosis in various human cancer cells. In the present study, we investigated further possible mechanisms by which ${\beta}$-lapachone exerts its pro-apoptotic action in cultured human lung cancer A549 cells. ${\beta}$-lapachone treatment resulted in inhibition of growth and induction of apoptosis in a concentration-dependent manner, as determined by MTT assay and flow cytometry analysis. The induction of apoptosis by ${\beta}$-lapachone was associated with up-regulation of the expression of p53 and p21 in both transcriptional and translational levels, and the phosphorylation of p53. In addition, ${\beta}$-lapachone activated caspase-3 and -9, and induced degradation of caspase-3 target proteins such as poly (ADP-ribose) polymerase (PARP) and ${\beta}$-catenin. Furthermore, ${\beta}$-lapachone treatment caused a progressive decrease in the expression levels of cyclooxygenase (COX)-2 without significant changes in the levels of COX-1, which was correlated with a decrease in prostaglandin E2 synthesis. Taken together, these results indicated that ${\beta}$-lapachone may have therapeutic potential in human lung cancer treatment.

• Journal of the Korean Society of Food Science and Nutrition
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• v.33 no.2
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• pp.455-462
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• 2004

Prostate cancer is a leading cause of cancer death in American men and evidences point to significant life style/diet components as risk factors for its development or prevention. Two large cohort studies have identified the consumption of tomatoes or high Plasma levels of Iycopene as associated with reduced risk. A number of other substances such as quercetin, phytoene, phytofluene, cyclolycopene, salicylates and tomatine in tomato besides lycopene could have anticancer activity and may be acting synergistically with lycopene. Lycopene at almost physiologically feasible concentrations, reduces cell viability by cell cycle arrest and apoptosis and modulates the cyclin pathways as well as increasing intercellular communication. However, it is not clear whether lycopene or its oxidation products are more bioactive. Tomato product supplementation results in plasma accumulation of phytoene, Phytofluene, the lycopene oxidation product, and cyclolycopene at significant concentrations and lycopene supplementation, either as a tomato product or as beadlets, results in maximal mean plasma lycopene concentrations of ∼ 1 $\mu$M which is at the lower limit of its activity in cell culture. Rats and mice are poor accumulators of lycopene and other carotenoids making them poor models for the study of cancer prevention and control. Of the 19 animal studies for various cancer sites, lycopene showed a positive effect in 10 studies but negative in 2 prostate cancer studies. In vivo prevention of leukocyte DNA damage in humans has been mostly studied using tomato product supplementation but lycopene supplementation appeared to reduce oxidative DNA damage as well as tomato product supplementation. Lycopene appears to be bioactive in intefering with carcinogenesis but the actions of phytoene, phytofluene or cyclolycopene cannot be ruled out since these compounds were present in most of the lycopene material used for these studies. Although lycopene remains as a promising agent, especially for cancer control, exploring interactions with other tomato phytochemicals and with current prostate cancer therapies should be encouraged.

• Biomolecules & Therapeutics
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• v.24 no.4
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• pp.363-370
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• 2016

Cardiovascular disease is the most common cause of death in diabetic patients. Hyperglycemia is the primary characteristic of diabetes and is associated with many complications. The role of hyperglycemia in the dysfunction of human cardiac progenitor cells that can regenerate damaged cardiac tissue has been investigated, but the exact mechanism underlying this association is not clear. Thus, we examined whether hyperglycemia could regulate mitochondrial dynamics and lead to cardiac progenitor cell dysfunction, and whether blocking glucose uptake could rescue this dysfunction. High glucose in cardiac progenitor cells results in reduced cell viability and decreased expression of cell cycle-related molecules, including CDK2 and cyclin E. A tube formation assay revealed that hyperglycemia led to a significant decrease in the tube-forming ability of cardiac progenitor cells. Fluorescent labeling of cardiac progenitor cell mitochondria revealed that hyperglycemia alters mitochondrial dynamics and increases expression of fission-related proteins, including Fis1 and Drp1. Moreover, we showed that specific blockage of GLUT1 improved cell viability, tube formation, and regulation of mitochondrial dynamics in cardiac progenitor cells. To our knowledge, this study is the first to demonstrate that high glucose leads to cardiac progenitor cell dysfunction through an increase in mitochondrial fission, and that a GLUT1 blocker can rescue cardiac progenitor cell dysfunction and downregulation of mitochondrial fission. Combined therapy with cardiac progenitor cells and a GLUT1 blocker may provide a novel strategy for cardiac progenitor cell therapy in cardiovascular disease patients with diabetes.

• Clinical and Experimental Pediatrics
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• v.49 no.10
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• pp.1100-1105
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• 2006

Purpose : Because NELL2 expression is strictly restricted only in neurons in developing and post-differentiated neural tissues, it is thought to be involved in the neuronal differentiation during development and in the maintenance of neuronal physiology in the post-differentiated neurons. In this study, we examined whether NELL2 is involved in the regulation of cell cycle and apoptosis in the hippocampal neuroprogenitor HiB5 cells. Methods : Effects of NELL2 on the cultured HiB5 cell numbers, DNA fragmentation, and proteins involved in the regulation of the cell cycle were measured. Results : NELL2 induced a decrease in cell numbers and an increase in G1 phase arrest. Moreover, transfection of NELL2 resulted in an increase of DNA fragmentation that shows an evidence of apoptosis. Contents of proteins involved in the regulation of cell cycle were also changed by transfection of NELL2 expression vectors. Conclusion : This study suggests that NELL2 plays an important role in the regulation of cell cycle and apoptosis of neurons.

• Journal of Life Science
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• v.14 no.5
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• pp.800-808
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• 2004

Resveratrol, a phytoalexin found at high levels in grapes and in grape products such as red wine, has been reported to possess a wide range of biological and pharmacological activities including antioxident, anti-inflammatory, anti-mutagenic, and anti-carcinogenic effects. According to recent studies, this compound is an effective inhibitor of cell growth in general, triggers partial arrest of the cell cycle and induce apoptosis. In this study, the anti-proliferative effects of resveratrol in A549 human lung carcinoma cells were investigated. It is shown that resveratrol induced the growth inhibition in a time-dependent manner and morphological changes of A549 cells, which were associated with induction of S phase arrest of the cell cycle and apoptotic cell death. The Bcl-$X_L$levels were markedly down-regulated in resveratrol treated cells, however, Bax and Bcl-2 were remained unchanged. Resveratrol treatment induced the proteolytic degradation of Sp-l and proliferating cell nuclear antigen protein, and inhibited the expression of $\beta$-catenin protein. Resveratrol treatment also induced a marked up-regulation of cyclin-dependent kinase (Cdk) inhibitor p21 and inhibited the kinase activities of Cdk2 and Cdk4. In addition, resveratrol treatment inhibited the levels of cyclooxygenase (COX)-2 mRNA and protein, and the release of prostagladin E2 without alteration of COX-1 expression. Taken together, these findings suggest that resveratrol may be a potential chemotherapeutic agent for the control of human lung carcinorma cells.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3757-3761
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• 2012

Objective: Crocin has been proposed as a promising candidate for cancer chemoprevention. The purpose of this investigation was to investigate the chemopreventive action and the possible mechanisms of crocin against human colon cancer cells in vitro. Methods: Cell proliferation was examined using MTT assay and the cell cycle distribution fractions were analyzed using fow cytometric analysis after propidium iodide staining. Apoptosis was detected using theTUNEL Apoptosis Detection Kit with laser scanning confocal microscope. DNA damage was assessed using the alkaline single-cell gel electrophoresis assay, while expression levels of p53, cdk2, cyclinA and P21 were examined by Western blot analysis. Results: Treatment of SW480 cells with crocetin (0.2, 0.4, 0.8 mmol/L) for 48 h signifcantly inhibited their proliferation in a concentration-dependent manner. Crocetin (0.8 mmol/L) signifcantly induced cell cycle arrest through p53-independent mechanisms accompanied by P21 induction. Crocetin (0.8 mmol/L) caused cytotoxicity in the SW480 cells by enhancing apoptosis and decreasing DNA repair capacity in a time-dependent manner. Conclusions: This report provides evidence that crocetin is a potential anticancer agent, which may be used as a chemotherapeutic drug.