• 생명과학회지
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• 제30권5호
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• pp.460-467
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• 2020

간암은 전 세계적으로 가장 높게 진단되는 암 중 하나이며, 방사선 및 화학 요법이 일반적으로 사용되는 치료법이지만 다양한 부작용은 치료 효과를 크게 제한한다. 따라서 전통 의학에서 사용되어 온 처방법은 이를 극복할 수 있는 대안이 될 수 있다. 본 연구에서는 동의보감에 기술되어 있는 3가지 한약 처방전(비기환, 대칠기탕 및 목향빈랑환)을 선택하여 인체 간암세포에 대한 항암 효과를 평가하였다. 간암세포에서 3가지 처방전의 에탄올 추출물의 세포 독성을 조사하기 위한 MTT 분석 결과, 비기환 추출물은 대칠기탕 및 목향빈랑환에 비하여 세포 생존력을 현저하게 억제하였다. 그리고, flow cytometry 분석의 결과에서 3가지 처방전 추출물에 의한 간암세포의 증식 억제가 apoptosis 및 autophagy 유도와 관련이 있었다. 특히, 비기환 추출물은 미토콘드리아의 기능을 크게 손상시켰으며 다른 두 처방전과 비교하여 mitophagy 유발 가능성을 보여주었다. 아울러 비기환 추출물은 LC3의 발현을 현저하게 증가시켰으며, 이는 Bcl-2의 발현 감소를 동반하는 반면, Bax의 발현에 영향을 미치지 않았다. PINK1의 발현 또한 비기환 추출물이 처리된 세포에서 매우 증가하였다. 나아가, autophagy 억제제는 3가지 처방전 추출물 처리에 의한 세포 생존율 감소와 apoptosis 유도를 억제하였으며, 이러한 결과는 이들 처방전 추출물 처리에 의한 autophagy가 apoptosis 개시에 관여하고 있음을 보여주는 것이다. 결론적으로, 본 연구 결과는 비기환 추출물이 3가지 처방전 중에서 가장 높은 항암 활성을 보였으며, 비기환 추출물은 autophagy 유도제로서 간암세포의 증식을 억제함을 의미한다.

• Asian Pacific Journal of Cancer Prevention
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• 제17권2호
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• pp.703-712
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• 2016

Monoclonal antibodies with specific antigens have been widely used as targeted therapy for cancer. Hep88 mAb is a monoclonal antibody which shows specific binding with anti-cancer effects against the HepG2 cell line. However, its mechanisms of action are still not completely understood. We examined cell cycling and apoptosis by flow cytometry and mRNA expression of factors involved in apoptosis and paraptosis in Hep88 mAb-treated HepG2 cells by real-time PCR. The cell-cycle analysis demonstrated that growth-inhibitory activity was associated with G2/M cell cycle arrest. Hep88 mAb induced a significant increase in apoptotic cell populations in a dose- and time-dependent manner. The mRNA expression results also suggested that the process triggered by Hep88 mAb involved up-regulation of tumor suppressor p53, pro-apoptotic Bax, Cathepsin B, Caspase-3 and Caspase-9, with a decrease of anti-apoptotic Bcl-2 - thus confirming paraptosis and apoptosis programmed cell death. These findings represent new insights into the molecular mechanisms underlying the anti-cancer properties of Hep88 mAb in liver cancer cells.

• Molecules and Cells
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• 제43권5호
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• pp.459-468
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• 2020

Nuclear receptor subfamily group H member 4 (NR1H4), also known as farnesoid X receptor, has been implicated in several cellular processes in the liver and intestine. Preclinical and clinical studies have suggested a role of NR1H4 in colon cancer development; however, how NR1H4 regulates colon cancer cell growth and survival remains unclear. We generated NR1H4 knockout (KO) colon cancer cells using clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein-9 nuclease (CAS9) technology and explored the effects of NR1H4 KO in colon cancer cell proliferation, survival, and apoptosis. Interestingly, NR1H4 KO cells showed impaired cell proliferation, reduced colony formation, and increased apoptotic cell death compared to control colon cancer cells. We identified MYC as an important mediator of the signaling pathway alterations induced by NR1H4 KO. NR1H4 silencing in colon cancer cells resulted in reduced MYC protein levels, while NR1H4 activation using an NR1H4 ligand, chenodeoxycholic acid, resulted in time- and dose-dependent MYC induction. Moreover, NR1H4 KO enhanced the anti-cancer effects of doxorubicin and cisplatin, supporting the role of MYC in the enhanced apoptosis observed in NR1H4 KO cells. Taken together, our findings suggest that modulating NR1H4 activity in colon cancer cells might be a promising alternative approach to treat cancer using MYC-targeting agents.

• 대한예방한의학회지
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• 제18권1호
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• pp.11-21
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• 2014

Objective : This study set out to combine the treatment efficacy of Taraxacum with Dongchimi fermentation and investigate Taraxacum's effects on protection of liver cell and controlling nitric oxide(NO) through experiments, thus checking whether it had values as a physiological active matter. The experimental materials include Taraxacum Dongchimi (TD) and Taraxacum fermented by Dongchimi (TDF). As for methodology, experiments were carried out to compare TD and TDF in components, protection effects for liver cells, anticancer effects on liver cells, and protection effects for brain cells in the aspects of liver function and immunity enhancement. Method : The experimental materials include Taraxacum Dongchimi (TD) and Taraxacum fermented by Dongchimi (TDF). As for methodology, experiments were carried out to compare TD and TDF in components, protection effects for liver cells, anti-cancer effects on liver cells, and protection effects for brain cells in the aspects of liver function and immunity enhancement. Results : As shown in the chromatogram results, each valid component content increased in Taraxacum fermented by Dongchimi (TDF) for each time section. Of them, the valid component content at 36.80 minutes was approximately 2.7 times higher in TDF at 21.8% than in Taraxacum Dongchimi (TD) at 8.28%. TDF generated more excellent protection effects against the toxicity that caused oxidative damage to the liver cell(HepG2) with t-BHP than TD. The survival rate was low in TD of $100{\mu}g/m{\ell}$ and $300{\mu}g/m{\ell}$ and increased to 23.3% in TDF of $100{\mu}g/m{\ell}$. The survival rate was the highest at $300{\mu}M$ with a significant difference of 68.1%(P<0.05). Both TD and TDF showed effects of controlling nitric oxide production according to concentration with TDF recording a higher rate of controlling nitric oxide production than TD. There were significant differences(P<0.05) in the effects of controlling nitric oxide production at 200 ug/ml, 400 ug/ml in both groups. Especially the result TDF of $400{\mu}g/m{\ell}$ was thus similar to those of butein, the positive control group. Conclusion : The result of this studies is that Taraxacum fermented by Dongchimi (TDF) increased the valid component content compared with the simple mixture(TD). The findings clearly show that it is a material with the effects of improving immunity and liver cell protection. If fermentation methods are further developed to use it as a functional material, it will be subject to more opportunities of being used in other functional foods and make a contribution to integrated medicinal food development.

• 대한약침학회지
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• 제5권1호
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• pp.61-79
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• 2002

Objective: The purpose of this study was to investigate acute and subacute toxicity and sarcoma-180 anti-cancer effects of Herbal acupuncture with Anneniacae amarum semen (Haeng-in) in mice and rats. Method: Balble mice were injected intraperitoneany with Haeng-In extract for $LD_{50}$ and acute toxicity test. Sprague-Dawley rats were injected intraperitoneally with Haeng-In extract for subacute toxicity test. TheAnneniacae amarum semen Herbal-Acupuncture was injected on Chung-wan (CV12) of mice with Sarcoma-180 cancer cell line. Results: 1. $LD_{50}$ was uncountable as none of the subjects expired from the treatment groups during the test. 2. The clinical signs and the body weight of mice treated with 0.1cc and 0.2cc Haeng-In extract were not affected during the acute toxicity test. 3. In acute toxicity test of serum biochemical values of mice, total protein and albumin were decreased in treatment group Ⅰ. Glucose was increased, and total cholesterol was decreased in treatment groups. GPT was increased in treatment group Ⅰ. 4. In subacute toxicity test, toxic symptoms were not detected in the treatment groups. 5. In subacute toxicity test, the body weight was increased in treatment groups on 14th and 21st day. 6. In subacute toxicity test. liver weight was increased in treatment group Ⅱ, and spleen weight was increased in treatment group Ⅱ. Lung weight was increased in an the treatment groups.(p<0.05) 7. In subacute toxicity test, severe tissue injury was found in lung and liver, especially treatment group Ⅰshowed more significant lung damage compared to treatment group l. 8. In subacute toxicity test, WBC. MCH and MCHC were increased in an the treatment groups, RBC, HGB and HCT were decreased in treatment group H(p<0.05). 9. In subacute toxicity test of serum biochemical values of rats, triglyceride was decreased in all the treatment groups. ALP was decreased in treatment group Ⅰ. and creatinine was decreased in treatment group Ⅱ. BUN/CR was increased in treatment group Ⅱ(p<0.05). 10. Median survival time of Sarcoma-180 cancer cell treated with Haeng-In was increased in all the treatment groups by twenty percent, compared to the control group(p<0.05). 11. Natural killer cell activity about the Sarcoma-180 cell was decreased at the ratio of 100:1 but was increased at the ratio of 10:1. In treatment group Ⅱ, increase was found at the ratio of 100:1 and 50:1 (p<0.05). 12. Interleukin-2 productivity of the Sarcoma-180 cell was decreased in treatment group I, but was increased in treatment group Ⅱ(p<0.05). Conclusion: According to the results, we can conclude Herbal-acupuncture with Anneniacae amarum semen caused toxicity, and had effects in Sarcoma-180 cancer cell.

• 대한한방내과학회지
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• 제29권3호
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• pp.582-594
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• 2008

Objective : The purpose of our study was to investigate the effect of JinlnWhaChul-tang-ga-wasong (JIN) on NDEA-induced liver tumorigenesis. Materials and Methods : We investigated the possible protective effects of Jininwhachul-tang-ga-wasong (JIN) as an anticancer against NDEA-induced liver injury in mice. Experimental mice were classified into 3 groups; normal, saline administered group (control group), and JIN extract (0.15g/kg/every other day) administered group (JIN group) after being injected with NDEA over 12 weeks. We examined the state of differentiation of these tumors and the effects of JIN after 6 weeks. To confirm the induction of apoptosis, the cells were analyzed by terminal deorynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay, acridine orange staining and flow cytometric analysis. To investigate inhibitory effect on the expression of COX-2 by JIN, we performed COX-2 immunohistochemistry and reverse transcription polymerase chain reaction analysis. Results : Body weights significantly decreased in the control and JIN groups compared with the normal group. The levels of cholesterol, hemoglobin and testosterone decreased in the control compared with the normal group. The level of estradiol significantly increased in the control compared with the normal group. The control group reacted with TUNEL assay more than the normal and JIN groups. Upon naked eye, light and electron microscopic examination, JIN improved the morphological and histopathological changes of the liver caused by NDEA-induced hepatic neoplasm. COX-2 immunoreactivity decreased in the JIN group compared with the control group, mRNA expression of the control group was greater than the normal and JIN groups. Conclusion : these results suggest the possibility that JIN may exert an anti-tumor effect on NDEA-induced liver tumorigenesis.

• 대한본초학회지
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• 제27권6호
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• pp.7-13
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• 2012

Objectives : Reactive oxygen species (ROS) have been associated with pathogenic processes including carcinogenesis through direct effect on DNA directly and by acting as a tumor promoter. Therefore, it has been regarded that ROS may be a major target for cancer prevention. The root of Paeonia lactiflora pall (PL), a traditional Chinese herb, has been a component of effective prescriptions for treatment of liver disease. Also, there are some reports about the antioxidant activities of the extracts from PL. However, little has been known about the effects of PL against oxidative damage. This work aimed to elucidate the anti-oxidant effects of Paeonia lactiflora pall (PL) in the non-cellular system and cellular system. Methods : Antioxidant activities of PL were evaluated by hydroxyl radical scavenging assay and $Fe^{2+}$ chelating assay. Anti-oxidative effect of PL was evaluated by ${\varphi}X$-174 RF I plasmid DNA cleavage assay in non-cellular system. In addition, DNA migration assay, expression level of phospho-H2AX, MTT assay and lipid peroxidation assay were performed for evaluate the anti-oxidative effect of PL in cellular system. Results : PL had a dose-dependent hydroxyl radical scavenging and $Fe^{2+}$ chelating capacity. In addition, PL inhibited oxidative DNA and cell damage induced by hydroxyl radical in non-cellular system and cellular system. Conclusion : Taken together, P. lactiflora pall may be possible for the application to a potential drug for treating the oxidative diseases such as cancer.

• 한국식품과학회지
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• 제50권4호
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• pp.451-456
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• 2018

본 연구는 사람유래 대장암세포가 이식된 동물모델을 사용하여 사리장의 항암효과를 확인하기 이하여 수행하였다. 사리장은 죽염과 서목태, 마늘과 유근피를 혼합 추출한 물질로써 아이소플라본을 포함하고 있으며 항염, 항산화 등의 효능이 보고된 물질이다. 이러한 사리장을 종양이 이식된 동물모델에 4주간 투여하면서 종양 크기의 변화, 종양 성장인자의 변화와 사리장의 안전성을 평가하였다. 그 결과 사리장은 종양의 크기를 감소시켰으며, 종양 성장과 관련된 ERK와 p16의 발현량을 조절함으로써 종양의 성장을 억제하는 효과를 나타냈다. 또한 사리장을 투여한 시험군에서는 체중, 장기무게, 혈청생화학적검사와 조직학적 검사에서 독성으로 인한 변화가 관찰되지 않았다. 이러한 결과는 사리장이 장기복용이 가능한 항암 보조식품의 소재로써 활용될 수 있다는 것을 의미한다고 할 수 있다.

• 셀메드
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• 제8권3호
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• pp.14.1-14.6
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• 2018

Santalum album Linn. [Family: Santalaceae] is commonly known as white sandalwood, sandal safaid and safed chandan. It is one of the most valuable trees and second costliest wood in the world. Sandalwood and its oil is extensively used in the Unani and other traditional systems of medicine as it has blood purifier, anti-inflammatory, analgesic, exhilarant, cardiotonic, antiseptic, nervine tonic and expectorant properties. It is used in skin, cardiac, liver, gastrointestinal, respiratory, integument and urogenital disorders. These uses are supported and proven by many in vitro or in vivo studies. The proven pharmacological activities of S. album are antimicrobial, anti-oxidant, anti-inflammatory, antimutagenic and anti-fatigue. The research has proven that sandal oil or its constituents have anti-microbial activity. Sandalwood oil showed skin cancer preventive effect in mice and its constituent alpha santalol showed the anticancer property. The methanolic extract of wood was confirmed for antioxidant, free radical scavenging, analgesic and anti-inflammatory activities. ${\alpha}$ and ${\beta}$ santalols present in sandal oil showed sedative effects. Sandalwood tea had a significant effect on heart muscles of frog and showed increased myocardial contractility. Its oil showed significant changes in hepatic xenobiotic metabolizing enzymes. Sandalwood oil and its major constituents showed less acute oral and dermal toxicity in laboratory animals. Hence, the aforementioned studies justify the uses of sandalwood and its oil mentioned in the classical Unani literature. However, further clinical trials are suggested to confirm its efficacy and safety in humans.

• Journal of Microbiology and Biotechnology
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• 제30권12호
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• pp.1896-1904
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• 2020

Muscle atrophy, characterized by a reduced number and size of myofibers, occurs due to immobilization, aging, and several chronic diseases. Leonurus japonicus, belonging to the Labiatae family, is widely used as a traditional medicine in Korea, China, and Japan. Previous studies have reported that L. japonicus has various physiological activities, such as anti-bacteria, anti-cancer, and liver protection. Leonurine, which is a major bioactive in L. japonicas, is known to possess biological effects including anti-inflammation, anti-fibrosis, anti-angiogenesis, and anti-diabetes. However, the preventive effects of L. japonicas and leonurine on muscle have not been reported. The current study aimed to determine the inhibitory effects of standardized L. japonicus extract (LJE) and leonurine on muscle atrophy by clarifying their underlying molecular mechanisms in tumor necrosis factor-alpha (TNF-α)-stimulated L6 myotubes. LJE and leonurine stimulated the phosphatidylinositol 3-kinase/Akt pathway that was reduced by TNF-α treatment. LJE and leonurine not only increased the mammalian target of rapamycin pathway for protein anabolism but also decreased the mRNA expression of E3 ubiquitin ligases by blocking the translocation of Forkhead box O, which is closely linked with proteolysis. Additionally, LJE and leonurine alleviated inflammatory responses by downregulating TNF-α and interleukin-6 mRNA expression and reducing the protein expression of nuclear factor-kappa B, a major transcriptional factor of proinflammatory cytokines. Collectively, LJE and leonurine have potential as therapeutic candidates for inhibiting the development of skeletal muscle atrophy by activating the PI3K/Akt pathway and reducing inflammatory responses.