• Journal of Ginseng Research
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• v.44 no.5
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• pp.725-737
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• 2020

Background: T-cell acute lymphoblastic leukemia (T-ALL) is a kind of aggressive hematological cancer, and the PI3K/Akt/mTOR signaling pathway is activated in most patients with T-ALL and responsible for poor prognosis. 20(S)-Ginsenoside Rh2 (20(S)-GRh2) is a major active compound extracted from ginseng, which exhibits anti-cancer effects. However, the underlying anticancer mechanisms of 20(S)-GRh2 targeting the PI3K/Akt/mTOR pathway in T-ALL have not been explored. Methods: Cell growth and cell cycle were determined to investigate the effect of 20(S)-GRh2 on ALL cells. PI3K/Akt/mTOR pathway-related proteins were detected in 20(S)-GRh2-treated Jurkat cells by immunoblotting. Antitumor effect of 20(S)-GRh2 against T-ALL was investigated in xenograft mice. The mechanisms of 20(S)-GRh2 against T-ALL were examined by cell proliferation, apoptosis, and autophagy. Results: In the present study, the results showed that 20(S)-GRh2 decreased cell growth and arrested cell cycle at the G1 phase in ALL cells. 20(S)-GRh2 induced apoptosis through enhancing reactive oxygen species generation and upregulating apoptosis-related proteins. 20(S)-GRh2 significantly elevated the levels of pEGFP-LC3 and autophagy-related proteins in Jurkat cells. Furthermore, the PI3K/Akt/mTOR signaling pathway was effectively blocked by 20(S)-GRh2. 20(S)-GRh2 suppressed cell proliferation and promoted apoptosis and autophagy by suppressing the PI3K/Akt/mTOR pathway in Jurkat cells. Finally, 20(S)-GRh2 alleviated symptoms of leukemia and reduced the number of white blood cells and CD3 staining in the spleen of xenograft mice, indicating antitumor effects against T-ALL in vivo. Conclusion: These findings indicate that 20(S)-GRh2 exhibits beneficial effects against T-ALL through the PI3K/Akt/mTOR pathway and could be a natural product of novel target for T-ALL therapy.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.1
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• pp.121-126
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• 2009

Korean ginseng (Panax ginseng C. A. Meyer) has been used as an important medicinal plant in the Orient for a long time. It has been claimed that ginseng has many beneficial bioactive effects on human health, such as antitumor, antistress, antiaging and enhancing immune functions. Red ginseng possibly have new ingredients converted during steaming and dry process from fresh ginseng. In this study, pharmacological efficacy and ingredient conversion of ginseng by 9 repetitive steaming and drying process were investigated measuring conversion efficiency of acidic-polysaccharide, phenolic compounds and inhibition of peroxide lipides. It was found that acidic-polysaccarides were increased by heat treatment. In addition, maltol of phenolic compounds, strong antioxidant, produced during the process of red ginseng by Maillard reaction. Acidic-polysaccarides and maltol were increased after the 1st and 3rd steaming and drying treatments, but they were decreased gradually after 5th, 7th, and 9th treatments. Antioxidant activity was increased as increasing treatment times of steaming and drying without significance. Effect of red ginseng extract on inhibition of peroxide was increased gradually until after the 7th treatment, but remarkably decreased after the 9th treatment.

• Biomolecules & Therapeutics
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• v.26 no.6
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• pp.591-598
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• 2018

Epigenetic silencing is considered to be a major mechanism for loss of activity in tumor suppressors. Reversal of epigenetic silencing by using inhibitors of DNA methyltransferase (DNMT) or histone deacetylases (HDACs) such as 5-Aza-CdR and FK228 has shown to enhance cytotoxic activities of several anticancer agents. This study aims to assess the combinatorial effects of genesilencing reversal agents (5-Aza-CdR and FK228) and oxaliplatin in gastric cancer cells, i.e., Epstein-Barr virus (EBV)-negative SNU-638 and EBV-positive SNU-719 cells. The doublet combinatorial treatment of 5-Aza-CdR and FK228 exhibited synergistic effects in both cell lines, and this was further corroborated by Zta expression induction in SNU-719 cells. Three drug combinations as 5-Aza-CdR/FK228 followed by oxaliplatin, however, resulted in antagonistic effects in both cell lines. Simultaneous treatment with FK228 and oxaliplatin induced synergistic and additive effects in SNU-638 and SNU-719 cells, respectively. Three drug combinations as 5-Aza-CdR prior to FK228/oxaliplatin, however, again resulted in antagonistic effects in both cell lines. This work demonstrated that efficacy of doublet synergistic combination using DNMT or HDACs inhibitors can be compromised by adding the third drug in pre- or post-treatment approach in gastric cancer cells. This implies that the development of clinical trial protocols for triplet combinations using gene-silencing reversal agents should be carefully evaluated in light of their potential antagonistic effects.

• IMMUNE NETWORK
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• v.10 no.4
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• pp.135-143
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• 2010

Background: Cordyceps militarys water extract (CME) has been reported to exert antitumor and immunomodulatory activities in vivo and in vitro. However, the therapeutic mechanism has not yet been elucidated. In this study, we examined the effects of CME on the antigen presenting function of antigen presenting cells (APCs). Methods: Dendritic cells (DCs) were cultured in the presence of CME, and then allowed to phagocytose microspheres containing ovalbumin (OVA). After washing and fixing the efficacy of OVA, peptide presentation by DCs were evaluated using CD8 and CD4 T cells. Also, we confirmed the protein levels of proinflammatory cytokines through western blot analysis. Results: CME enhanced both MHC class I and class II-restricted presentation of OVA in DCs. In addition, the expression of both MHC class I and II molecules was enhanced, but there was no changes in the phagocytic activity of exogenous OVA. Furthermore, CME induced the protein levels of iNOS, COX-2, proinflammatory cytokines, and nuclear p65 in a concentration-dependent manner, as determined by western blot. Conclusion: These results provide an understanding of the mechanism of the immuno-enhancing activity of CME on the induction of MHC-restricted antigen presentation in relation to their actions on APCs.

• Korean Journal of Pharmacognosy
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• v.8 no.1
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• pp.1-15
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• 1977

In an attempt to deduce which plants might have been used for their anticancer activities in traditional oriental herb medicine, 127 prescriptions were selected from 'Dong-Eui-Bo-Gam', the Classic Handbook of Korean Traditional Medicine, written by $H_{UH}$ Jun and published in 1613. These are the prescriptions indicated for the systemic treatment of various tumors and some conditions resembling tumors, e.g. inflammatory masses and indurations, and they include 150 natural products of plant origin. The frequency of appearance of each medicinal plant in these selected prescriptions was compared with the frequency of its appearance in all prescriptions listed in 'Bang-Yak-Hap-Pyon', another popular Oriental Medicine Formulary in Korea, written by $H_{WANG}\;Pil-Su$ in 1885. From the latter book, $H_{ONG}$ has recently enumerated frequencies of 235 medicinal plants included in a total of 467 prescriptions. Chi-square tests revealed that 11 plant remedies appear with significantly higher frequency in the prescriptions for "tumors", and 10 for "inflammations". The plants with potential antitumor activities, in decreasing order of statistical significance, are Scirpus maritimus, Curcuma zedoaria, Prunus persica, Rheum coreanum, Foeniculum vulgare, Rhus vernifera, Daphne pseudogenkwa, Galarhaeus sieboldiana, Croton tiglium, Raphanus sativus and Galarhaeus pekinensis. The drugs for potential antibacterial or anti-inflammatory activities are Olibanum(Frankincense), Forsythia coreana, Lonicera japonica, Gleditchia officinalis, $M_{YRRH}$, Trichosanhes kirilowii, Astragalus membranaceus, Rheum coreanum, Platycodon grandiflorum and Fritillaria verticillata. Despite the uncertainties involved in the terminology of various diseases used in pre-modern medicine, and the reservations about the efficacy of remedies used for those diseases, it would be worthwhile to investigate these few selected plants for anticancer, antibacterial, anti-inflammatory or antifungal effects, employing modern scientific methodology.

• Radiation Oncology Journal
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• v.34 no.3
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• pp.230-238
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• 2016

Purpose: Hypoxia can impair the therapeutic efficacy of radiotherapy (RT). Therefore, a new strategy is necessary for enhancing the response to RT. In this study, we investigated whether the combination of nanoparticles and RT is effective in eliminating the radioresistance of hypoxic tumors. Materials and Methods: Gold nanoparticles (GNPs) consisting of a silica core with a gold shell were used. CT26 colon cancer mouse model was developed to study whether the combination of RT and GNPs reduced hypoxia-induced radioresistance. Hypoxia inducible $factor-1{\alpha}$ ($HIF-1{\alpha}$) was used as a hypoxia marker. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were conducted to evaluate cell death. Results: Hypoxic tumor cells had an impaired response to RT. GNPs combined with RT enhanced anti-tumor effect in hypoxic tumor compared with RT alone. The combination of GNPs and RT decreased tumor cell viability compare to RT alone in vitro. Under hypoxia, tumors treated with GNPs + RT showed a higher response than that shown by tumors treated with RT alone. When a reactive oxygen species (ROS) scavenger was added, the enhanced antitumor effect of GNPs + RT was diminished. Conclusion: In the present study, hypoxic tumors treated with GNPs + RT showed favorable responses, which might be attributable to the ROS production induced by GNPs + RT. Taken together, GNPs combined with RT seems to be potential modality for enhancing the response to RT in hypoxic tumors.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.2409-2414
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• 2012

Objective: Traditional Chinese herbal medicines have a very long history. Rosa roxburghii Tratt and Fagopyrum cymosum are two examples of plants which are reputed to have benefits in improving immune responses, enhancing digestive ability and demonstrating anti-aging effects. Some evidence indicates that herbal medicine soups containing extracts from the two in combination have efficacy in treating malignant tumors. However, the underlying mechanisms are far from well understood. The present study was therefore undertaken to evaluate anticancer effects and explore molecular mechanisms in vitro. Methods: Proliferation and apoptosis were assessed with three carcinoma cell lines (human esophageal squamous carcinoma CaEs-17, human gastric carcinoma SGC-7901 and pulmonary carcinoma A549) by MTT assay and flow cytometry, respectively, after exposure to extract from Rosa roxburghii Tratt (CL) and extract from Fagopyrum cymosum (FR). $IC_{30}$ of CL and FR were obtained by MTT assay. Tumor cells were divided into four groups : control with no exposure to CL or FR; CL with $IC_{30}$ CL; FR with $IC_{30}$ FR; CL+FR group with 1/2 ($IC_{30}$ CL + $IC_{30}$ FR). RT-PCR and Western blot analysis were used to detect the expression of Ki-67, Bax and Bcl-2 at mRNA and protein levels. Results: Compared with the CL or FR groups, the combination of CL+FR showed significant inhibition of cell growth and increase in apoptosis; the mRNA and protein expression levels of Ki-67 and Bcl-2 in CL+FR group were all greatly decreased, while the expression of Bax was markedly increased. Conclusions: These results indicate that the synergistic antitumor effects of combination of CL and FR are related to inhibition of proliferation and induction of apoptosis.

• Natural Product Sciences
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• v.12 no.4
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• pp.247-253
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• 2006

The antitumor activity of crude saponin mixture obtained from Luffa tuberosa (Roxb.) (Fam; Cucurbitaceae) hairy roots (CSLT) in mice transplanted with Ehrlich ascites carcinoma (EAC) was investigated. The EAC-bearing mice receiving 150 and $300{\mu}g/kg$ body weight, (i.p) of CSLT have shown a dose dependent elevation in tumor-tree survival and a highest number of survivors were observed after administration of CSLT $(300{\mu}g/kg)$, which was considered as an optimum dose for its antineoplastic action. The mean survival time (MST) for this dose was approximately $47.1{\pm}0.74d$, when compared with $19.0{\pm}0.36d$ of untreated control. Administration of $300{\mu}g/kg$ CSLT resulted in 130% long-term increased survival time. The measurement of body weight, tumor volume, packed cell volume, viable and non-viable count indicated the efficacy of CSLT in tumor-bearing mice, there was a significant recovery in hematological profiles, and there was depletion in lipid peroxidation levels, and the antioxidant enzyme activities such as GSH, SOD and CAT were restored to near the normal levels. The CSLT was found to be devoid of conspicuous short-term toxicity in the mice when animals were intraperitoneally injected with 250, 500, 750 and $1000{\mu}g/kg$ bodyweight. The treated mice showed conspicuous toxic symptoms only at a dose of $1500{\mu}g/kg$. Mortality of the animals was monitored up to 14 d post drug treatment, $1/7^{th}$ of the $LD_{50}$ dose has been considered for the optimal antineoplastic activity.

• Journal of dental hygiene science
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• v.18 no.3
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• pp.188-193
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• 2018

The aim of the current study was to demonstrate the potential therapeutic efficacy of resveratrol in oral cancer patients. Lysophosphatidic acid (LPA) intensifies cancer cell invasion and metastasis, whereas resveratrol, a natural polyphenolic compound, possesses antitumor activity, suppressing cell proliferation and progression in various cancer cell lines (ovarian, gastric, oral, pancreatic, colon, and prostate cancer cells). In addition, resveratrol has been identified as an inhibitor of LPA-induced proteolytic enzyme expression and ovarian cancer invasion. Furthermore, resveratrol was shown to inhibit oral cancer cell invasion by downregulating hypoxia-inducible factor $1{\alpha}$ and vascular endothelial growth factor expression. Recently, we demonstrated that LPA is important for the expression of transcription factors TWIST and SLUG during epithelial-mesenchymal transition (EMT) in oral squamous carcinoma cells. In this study, we treated serum-starved cultures of oral squamous carcinoma cell line YD-10B with resveratrol for 24 hours prior to stimulation with LPA. To identify an optimal resveratrol concentration that does not induce apoptosis in oral squamous carcinoma cells, we determined the toxicity of resveratrol in YD-10B cells by assessing their viability using the MTT assay. Another assay was performed using Matrigel-coated cell culture inserts to detect oral cancer cell invasion activity. Immunoblotting was applied for analyzing protein expression of SLUG, TWIST1, E-cadherin, and GAPDH. We demonstrated that resveratrol efficiently inhibited LPA-induced oral cancer cell EMT and invasion by downregulating SLUG and TWIST1 expression. Therefore, resveratrol may potentially reduce oral squamous carcinoma cell invasion and metastasis in oral cancer patients, improving their survival outcomes. In summary, we identified new targets for the development of therapies against oral cancer progression and characterized the therapeutic potential of resveratrol for the treatment of oral cancer patients.

• The Korean Journal of Pain
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• v.25 no.1
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• pp.1-6
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• 2012

Background: Curcumin has been reported to have anti-inflammatory, antioxidant, antiviral, antifungal, antitumor, and antinociceptive activity when administered systemically. We investigated the analgesic efficacy of intrathecal curcumin in a rat model of inflammatory pain. Methods: Male Sprague Dawley rats were prepared for intrathecal catheterization. Pain was evoked by injection of formalin solution (5%, $50{\mu}l$) into the hind paw. Curcumin doses of 62.5, 125, 250, and $500{\mu}g$were delivered through an intrathecal catheter to examine the flinching responses. The $ED_{50}$ values (half-maximal effective dose) with 95% confidence intervals of curcumin for both phases of the formalin test were calculated from the dose-response lines fitted by least-squares linear regression on a log scale. Results: In rats with intrathecal administration of curcumin, the flinching responses were significantly decreased in both phases. The slope of the regression line was significantly different from zero only in phase 2, and the $ED_{50}$ value (95% confidence interval) of curcumin was $511.4{\mu}g$ (23.5-1126.5). There was no apparent abnormal behavior following the administration of curcumin. Conclusions: Intrathecal administration of curcumin decreased inflammatory pain in rats, and further investigation to elucidate the precise mechanism of spinal action of curcumin is warranted.