• Journal of Oral Medicine and Pain
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• v.35 no.3
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• pp.165-175
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• 2010

Valproic acid (VPA) is a well-known anticonvulsive agent and has been used in the treatment of epilepsy for almost 30 years. VPA emerged in 1997 as an antineoplastic agent as well, when findings indicated the substance inhibited proliferation and induced differentiation of primitive neuroectocdermal tumor cells in vivo (Cinatl et al., 1997). Antitmor activity of VPA is associated with its targeting histone deacetylases. Bile acids and their synthetic derivatives induced apoptosis in various kinds of cancer cells and anticancer effects. It has been reported that the synthetic chenodeoxycholic acid (CDCA) derivatives showed apoptosis-inducing activity on various cancer cells in vitro. This study was undertaken to investigate the synergistic apoptotic effect of co-treatment with the histone deacetylases inhibitor, VPA and a CDCA derivative, HS-1200 on human osteosarcoma (HOS) cells. Cell viability was evaluated by trypan-blue exclusion. Induction and augmentation of apoptosis were confirmed by Hoechst staining, flow cytometry (DNA hypoploidy and MMP change), Westen blot analysis and immunofluorescent staining. In this study, HOS cells co-treated with VPA and HS-1200 showed several lines of apoptotic manifestation such as nuclear condensations, the reduction of MMP, the decrease of DNA content, the release of cytochrome c into cytosol, the translocation of AIF onto nuclei, and activation of caspase-7, caspase-3 and PARP whereas each single treated HOS cells did not. Although the single treatment of 1 mM VPA or $25\;{\mu}M$ HS-1200 for 48 h did not induce apoptosis, the co-treatment of them induced prominently apoptosis. Therefore our data provide the possibility that combination therapy of VPA and HS-1200 could be considered as a novel therapeutic strategy for human osteosarcoma.

• Journal of the Korean Society of Food Science and Nutrition
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• v.38 no.1
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• pp.25-31
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• 2009

This study was carried out to investigate the mutagenic, antimutagenic, cytotoxicity and antitumor effects of Adenophora triphylla (AT). AT was extracted with 70% ethanol and then further fractionated to hexane, chloroform, ethyl acetate, butanol and water. Antimutagenic, cytotoxicity and antitumor effects of AT extracts were measured by using Ames test, SRB method, and the tumor growth inhibition test. AT extracts did not show any mutagenicity in the Ames test; however, 70% ethanol extracts and its fractions had strong antimutagenic effects against mutation induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and 4-nitroquinoline-1-oxide (4NQO). The ethyl acetate fraction of AT (200 ${\mu}g$/plate) showed approximately 66.5% inhibitory effect on the mutagenesis induced by 4NQO against TA98 strain, whereas 83.3% and 75.1% inhibitions were observed on the mutagenesis induced by MNNG and 4NQO against TA100 strain. In anticancer effects, the cytotoxicity of AT extract and its fractions against cancer cell lines including human cervical adenocarcinoma (HeLa), human hepatocellular carcinoma (Hep3B), human breast adenocarcinoma (MCF-7), human gastric carcinoma (AGS), human lung carcinoma (A549) and transformed primary human embryo kidney (293) were investigated. The treatment of 1 mg/mL AT ethyl acetate faction had the highest cytotoxicity of 79.9%, 74.9%, 66.0%, 71.0% and 74.3% against HeLa, Hep3B, MCF-7, AGS and A549 cells, respectively. In contrast, the extract and its fractions showed only $3{\sim}36%$ cytotoxicity for a normal human kidney cell line (293). In vivo anti-cancer effect of Adenophora triphylla extract was tested using Balb/c mice transplanted sarcoma-180 cells. Adenophora triphylla ethyl acetate fraction showed the highest inhibition rate of 37.2% at the 50 mg/kg concentration.

• Korean Journal of Plant Resources
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• v.33 no.4
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• pp.227-236
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• 2020

Panax ginseng C.A. Meyer (P. ginseng) is known to exert a wide range of pharmacological effects both in vitro and in vivo. Although studies on ginsenoside, antioxidant activity, and anticancer effect of the cultivated wild Panax ginseng (CWP) have been conducted, there is little research on the effect of CWP extract on bone metabolism. In this study, we investigated the potential anti-osteoporotic properties of CWP on the growth and differentiation of MC3T3-E1 cells. CWP significantly increased the viability and proliferation of MC3T3-E1 cells. CWP activated intracellular alkaline phosphatase (ALP) activity in MC3T3-E1 cells. In addition, CWP increased the mineralized nodules in MC3T3-E1 cells. Furthermore, CWP increased the expression of genes such as Runx2, ALP, OPN and OCN associated with osteoblast growth and differentiation in a dose-dependent manner.

• Journal of the Korean Society of Food Science and Nutrition
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• v.42 no.4
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• pp.520-526
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• 2013

To determine the kimchi with the best quality and functional characteristics, we manufactured and compared recipes for Korean and Japanese kimchi made either Korean or Japanese baechu cabbages. All batches were fermented for 4 weeks at $5^{\circ}C$, and tested for pH, texture, microbial count, sensory evaluation, DPPH radical-scavenging activity, and cell proliferation (using the MTT assay on AGS human gastric cancer cells). By the third week of fermentation, Korean kimchi made with Korean baechu (KK) and Japanese kimchi made with Korean baechu (KJ) showed a higher acidity than Korean or Japanese kimchi made with Japanese baechu (JK and JJ, respectively). KK ranked highest in springiness, followed by KJ, JK, and JJ. Therefore, the texture of kimchi produced with Korean baechu was appears better than kimchi produced with Japanese baechu. This was confirmed in masticatory tests. Kimchi produced with Korean baechu (KK and KJ) showed lower total aerobic bacterial counts, while the total lactic acid bacterial counts were higher (p<0.05). In sensory evaluation test, KK received the highest overall acceptability score, while JJ earned the lowest score. In the DPPH assay for anti-oxidative activity, KK showed a 94% anti-oxidative effect, followed by KJ (92%), JK (91%), and JJ (88%) (p<0.05). In the MTT assay for analyzing the cell proliferation of AGS human gastric cancer cells, KK showed a 64% anticancer effect in vitro, followed by KJ (57%), JK (38%), and JJ (26%). Therefore, the anti-oxidative and anti-cancer functionalities of kimchi made with Korean baechu were higher than those made with Japanese baechu, regardless of the kimchi recipe applied. Overall, Korean baechu had important and superior effects on the quality and functionality of kimchi.

• Journal of Nutrition and Health
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• v.42 no.7
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• pp.605-614
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• 2009

Most cancer patients are treated with surgery, chemotherapy or radiation as anticancer therapies. Especially in the case of radiation, these treatments produce adverse effects such as vomiting, weight loss, anorexia, normal cell damage and malabsorption. The major goal of this study was to determine the effect of irradiation on the nutritional and immune status in irradiated rats. A secondary goal was to determine the effectiveness of high protein diet (HP) and resveratrol (Res) in minimizing the adverse effects of radiation. Rats were divided into four groups: normal diet (NP), HP, NP + Res and HP + Res groups. Each group was further divided into subgroups that received radiation (RT group) and one that did not (non-RT group). Each diet was supplied from $12^{th}$ day prior to irradiation treatment with irradiation dose of 17.5 Gy. The diets were continued until 10th day after radiation treatment and animals were sacrificed. The radiation treatment showed decreased body weight, serum protein and HDL levels and increased TG and LDL levels in nutritional status. HP, NP + Res and HP + Res groups reduced the level of serum LDL and TG in irradiated rats. NP + Res and HP + Res groups increased reduced albumin level of serum in RT group. In case of immune status, the radiation treat-ment showed decreased WBC, lymphocytes and increased neutrophil and eosinophil levels. The levels of serum IL-2 and IL-6 were significantly increased by radiation, however the cytokine levels decreased in all dietary treatment groups. These results showed that high protein diet and resveratrol supplementation seem to minimize the adverse effects of radiation on lipid nutritional status and inflammation response in the rat model.

• Korean Journal of Medicinal Crop Science
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• v.10 no.2
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• pp.132-138
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• 2002

This study was performed to determine the antimutagenic and cytotoxic effect of ,Kalopanacis cortex endothelium. Methanol extract was used on Salmonella typhimurium TA98, TA100 and three cancer cell lines. In the Ames test, methanol extract of Kalopanacis cortex endothelium alone did not exhibit any mutagenicity but showed substantial inhibitory effects against mutation induced by 4-nitroquinoline-l-oxide(4NQO), N'-methyl- N'-nitro-N-nitrosoguanidine(MNNG) and benzo(a)pyrene(B(a)P). The methanol extract of Kalopanacis cortex endothelium showed approximately 79.29% and 75.38% inhibitory effect on the mutagenesis induced by 4NQO and B(a)P, respectively, against TA98 strain. Whereas 79.49%, 89.3% and 68.85% inhibitions were observed on the mutagenesis induced by 4NQO, MNNG and B(a)P against TA100 strain. Methanol extracts from Kalopanacis cortex endothelium showed high antimutagenic effects against 4NQO, MNNG and B(a)P. The anticancer effects of methanol extract from Kalopanacis cortex endothelium against human lung carcinoma(A549), human breast adenocarcinoma (MCF-7) and human hepatocellular carcinoma(Hep3B) were investigated. The treatment of 0.5mg/ml Kalopanacis cortex endothelium methanol extracts had the highest cytotoxicity against A549(81.54%), followed by MCF-7(81.92%) and Hep3B (78.57%). In contrast 0.5mg/ml treatment of methanol extracts from Kalopanacis cortex endothelium had only $4{\sim}25%$ cytotoxicity on normal human liver cell(293).

• Journal of Life Science
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• v.23 no.5
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• pp.689-697
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• 2013

In the United States, about 40,000 new cases of oral cancer are diagnosed each year and nearly 7,800 patients died from it in 2012. Omega-3 polyunsaturated fatty acids have been found to have anticancer effects in a variety of cancer cell lines and animal models, but their effect in oral cancer remains unclear. This study was designed to examine the effect of docosahexaenoic acid (DHA, a kind of omega-3 fatty acid) on oral cancer cells and the molecular mechanism of its action. We found that exposure of squamous cell carcinoma-4 (SCC-4) and squamous cell carcinoma-9 (SCC-9) human oral cancer cells to DHA induced growth inhibition in a dose- and time-dependent manner. Meanwhile, in addition to the elevated levels of apoptotic markers, such as cleaved PARP, subG1 portion and TUNEL-positive nuclei, DHA led to autophagic vesicle formation and an increase in autophagic flux, indicating the involvement of both apoptosis and autophagy in the inhibitory effects of DHA on oral cancer cells. Further experiments revealed that the apoptosis and autophagy induced by DHA were linked to inhibition of mammalian target of rapamycin (mTOR) signaling by AKT inhibition and AMP-activated protein kinase (AMPK) activation in SCC-9 cells. Together, our results suggest that DHA induces apoptosis- and autophagy-associated cell death through the AMPK/AKT/mTOR signaling pathway in oral cancer cells. Thus, utilization of omega-3 fatty acids may represent a promising therapeutic approach for chemoprevention and treatment of human oral cancer.

• Journal of Oral Medicine and Pain
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• v.32 no.3
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• pp.251-261
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• 2007

Bile acids and synthetic its derivatives induced apoptosis in various kinds of cancer cells and anticancer effects. Previous studies have been reported that the synthetic chenodeoxycholic acid (CDCA) derivatives showed apoptosis inducing activity on various cancer cells in vitro. It wasn't discovered those materials have apoptosis induced effects on YD9 human oral squamous carcinoma cells. The present study was done to examine the synthetic bile acid derivatives(HS-1199, HS-1200) induced apoptosis on YD9 cells and such these apoptosis events. We administered them in culture to YD9 cells. Tested YD9 cells showed several lines of apoptotic manifestation such as activation of caspase-3, degradation of DFF, production of poly (ADP-ribose) polymerase(PARP) cleavage(HS-1200 only), DNA degradation(HS-1200 only), nuclear condensation, inhibition of proteasome activity, reduction of mitochondrial membrane potential(HS-1200 only) and the release of cytochrome c and AIF to cytosol. Between two synthetic CDCA derivatives, HS-1200 showed stronger apoptosis-inducing effect than HS-1199. Therefore HS-1200 was demonstrated to have the most efficient antitumor effect. Taken collectively, we demonstrated that a synthetic CDCA derivative HS-1200 induced caspases-dependent apoptosis via mitochondrial pathway in human oral sqauamous carcinoma cells in vitro. Our data therefore provide the possibility that HS-1200 could be considered as a novel therapeutic strategy for human orall squamous carcinoma from its poweful apoptosis-inducing activity.

• Journal of Life Science
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• v.29 no.4
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• pp.410-420
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• 2019

Citrus unshiu peel extracts possess a variety of beneficial effects, and studies on their anticancer activity have been reported. However, the exact mechanisms underlying this activity remain unclear. In the current study, the apoptotic effect of ethanol extract of C. unshiu peel (EECU) on human breast adenocarcinoma MDA-MB-231 cells and related mechanisms were investigated. The results showed that the survival rate of MDA-MB-231 cells treated with EECU was significantly inhibited in a concentration-dependent manner, which was associated with the induction of apoptosis. EECU-induced apoptosis was associated with the activation of caspase-8 and caspase-9, which initiate extrinsic and intrinsic apoptosis pathways, respectively, and caspase-3, a representative effect caspase. EECU suppressed the expression of the inhibitor of apoptosis family of proteins, leading to an increased Bax/Bcl-2 ratio and proteolytic degradation of poly (ADP-ribose) polymerase. EECU also enhanced the loss of the mitochondrial membrane potential and cytochrome c release from the mitochondria to the cytosol, along with truncation of Bid. In addition, EECU activated AMP-activated protein kinase (AMPK), and compound C, an AMPK inhibitor, significantly weakened EECU-induced apoptosis and cell viability reduction. Furthermore, EECU promoted the generation of reactive oxygen species (ROS), which acted as upstream signals for AMPK activation as pretreatment of cells, with the antioxidant N-acetyl cysteine reversing both EECU-induced AMPK activation and apoptosis. Collectively, these findings suggest that EECU inhibits MDA-MB-231 adenocarcinoma cell proliferation by activating intrinsic and extrinsic apoptotic pathways, which was mediated through ROS/AMPK-dependent pathways.

• Journal of agriculture & life science
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• v.53 no.5
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• pp.127-136
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• 2019

Today, as the specification of pigs increases, it is important to develop eco-friendly livestock feeds that do not add antibiotics to highly utilizable materials as feed resources, and to produce functional eco-friendly pork and processed products. The purpose of this study was to establish Rubus occidentalis (RO) byproducts containing various amounts of physiologically active substances such as anticancer, anti - inflammation and antioxidant as a raw material for pig feed. The multifaceted efficacy of the RO fermented fodder (ROFF) was confirmed by the nutrient transport factors and antioxidant activity of Berkshire pigs. ROFF was added 0.3% to the general diet and the efficacy was confirmed by feeding diets to Berkshire pigs according to each weight for 43~73 days. As a result, the total cholesterol (TC), LDL-cholesterol (LDL-C) and HDL-cholesterol (HDL-C) levels were decreased or were increased in the castrated male and female Berkshire pigs but not significantly. It was confirmed that the tendency was improved in nutrition physiology. The biochemical levels of female finishing pigs were not significant but increased. In the case of finishing pigs with possibility of pregnancy, it is expected that the nutrition supply for piglet production and will help in the production of the healthy piglet. Transferrin (TFE) levels tended to increase in female growing pig and 110-150 kg finishing pigs. Thus ROFF could minimize the negative effects of iron contents deficiency in female Berkshire pigs. Glutathione peroxidase 1 (GPx1) activity was increased in castrated male and female 110-150 kg finishing pigs. Therefore, ROFF tends to improve the antioxidant capacity. The results of this study suggest that ROFF is one of the most favorable dietary sources when considering the contents of RO in feed. In particular, ROFF could have a positive effect on nutrient transport and iron content of female rather than castrated male Berkshire pigs.