• Journal of Microbiology and Biotechnology
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• 제31권11호
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• pp.1576-1582
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• 2021

Bacterial β-glucuronidase in the intestine is involved in the conversion of 7-ethyl-10-hydroxycamptochecin glucuronide (derived from irinotecan) to 7-ethyl-10-hydroxycamptothecin, which causes intestinal bleeding and diarrhea (side effects of anti-cancer drugs). Twelve compounds (1-12) from Polygala tenuifolia were evaluated in terms of β-glucuronidase inhibition in vitro. 4-O-Benzoyl-3'-O-(O-methylsinapoyl) sucrose (C3) was highly inhibitory at low concentrations. C3 (an uncompetitive inhibitor) exhibited a k_i value of 13.4 μM; inhibitory activity increased as the substrate concentration rose. Molecular simulation revealed that C3 bound principally to the Gln158-Tyr160 enzyme loop. Thus, C3 will serve as a lead compound for development of new β-glucuronidase inhibitors.

• 대한본초학회지
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• 제39권5호
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• pp.9-17
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• 2024

Objectives : Edible insects are the widely distributed group of animals and contain high quality proteins, fatty acids and minerals. In particular, insects are a possible interesting source of essential amino acids. Insects as traditional medicines have much potential as pharmaceuticals in modern medicines including treating infections, cancer, dissolving phlegm, relieving spasms, and inflammatory diseases. The aim of this study is to investigate the immunomodulatory effect of several kinds of insects and major amino acids. Methods : In our review we try to show the potential usefulness of insects and amino acids in searching for new therapeutic solutions for immunologic diseases. We summarized the knowledge about properties, usefulness of insect and amino acids in drug design. We hypothesized that insects and amino acids, their major ingredients, regulates airway inflammation and immunologic diseases and can be developed as therapeutic drugs for the treatment of immunologic diseases. Results : Several insects including Bombyx mori, Cryptotympana pustulata, Holotrichia diomphalia, Locusta migratoria, etc. and amino acids such as glutamine, glutamic acid, methionine and glycine may have potential protective effects against asthma and airway neutrophilia. Glutamic acid, cystine, methionine and glycine which contribute to glutathione metabolism, which are important anti-oxidant amino acids that may affect susceptibility to asthma. Conclusions : Our results provide evidence about the potential usefulness of several insects and their amino acids in allergic disorders. These findings suggest that several insects and amino acids have important roles in the way they affect the immune system and allergic responses.

• Journal of Applied Biological Chemistry
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• 제58권3호
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• pp.219-226
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• 2015

본 연구에서는 레몬 잎 메탄올 추출물(MLL)의 인간 유방암 줄기 세포인 MCF-7-SC에 대한 항암 활성을 조사하였다. MLL이 MCF-7-SC에서 apoptosis를 유도하였으며, 이를 apoptotic body의 형성, sub-G1 phase 및 annexin V-positive 세포와 Bax/Bcl-2 ratio의 증가, caspase-9과 caspase-3의 활성화 및 PARP의 절 단을 통하여 확인하였다. 동시에 MCF-7-SC에서 MLL은 acidic vesicular organelles의 형성, LC3-II의 축적 증가, Akt/mTOR/p70S6K의 활성 억제 등을 통하여 autophagy를 유도하였다. Epithelial-mesenchymal transition (EMT)는 세포가 전이 상태를 획득하기 위한 중요한 과정이며, 이 기작은 암세포가 전이되는 것을 억제함에 있어서 중요한 표적이 된다. 낮은 농도에서의 MLL은 epithelial 마커 단백질인 E-cadherin이 증가와 mesenchymal 마커 단백질인 Snail과 Slug의 발현 감소를 통해 EMT 과정을 저해함으로써 MCF-7-SC에서 항전이 활성을 나타내었다. 본 연구에서는 레몬 잎 메탄올 추출물이 농도 의존적으로 유방암 줄기세포에 대해 세포 독성과 항전이 활성을 나타내고 있으며, 따라서 레몬잎은 항암 소재로서의 개발 가능성이 높은 식물이라고 사료된다.

• Toxicological Research
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• 제34권2호
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• pp.133-141
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• 2018

Anti-cancer drugs such as cisplatin and doxorubicin are effectively used more than radiotherapy. Cisplatin is a chemotherapeutic drug, used for treatment of various forms of cancer. However, it has side effects such as ototoxicity and nephrotoxicity. Cisplatin-induced nephrotoxicity increases tubular damage and renal dysfunction. Consequently, we investigated the beneficial effect of cynaroside on cisplatin-induced kidney injury using HK-2 cell (human proximal tubule cell line) and an animal model. Results indicated that $10{\mu}M$ cynaroside diminished cisplatin-induced apoptosis, mitochondrial dysfunction and caspase-3 activation, cisplatin-induced upregulation of caspase-3/MST-1 pathway decreased by treatment of cynaroside in HK-2 cells. To confirm the effect of cynaroside on cisplatin-induced kidney injury in vivo, we used cisplatin exposure animal model (20 mg/kg, balb/c mice, i.p., once a day for 3 days). Renal dysfunction, tubular damage and neutrophilia induced by cisplatin injection were decreased by cynaroside (10 mg/kg, i.p., once a day for 3 days). Results indicated that cynaroside decreased cisplatin-induced kidney injury in vitro and in vivo, and it could be used for improving cisplatin-induced side effects. However, further experiments are required regarding toxicity by high dose cynaroside and caspase-3/MST-1-linked signal transduction in the animal model.

• Asian Pacific Journal of Cancer Prevention
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• 제15권6호
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• pp.2619-2623
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• 2014

Aim: To investigate signaling pathways for reversal of EGF-mediated multi-drug resistance (MDR) in hepatocellular carcinoma (HCC) models. Materials and Methods: HCC MDR cell strain HepG2/adriamycin (ADM) and SMMC7721/ADM models were established using a method of exposure to medium with ADM between low and high concentration with gradually increasing concentration. Drug sensitivity and reversal of multi-drug resistance by EGF were determined and the cell cycle distribution and apoptosis were analyzed by flow cytometry. Phosphorylation of ERK1, ERK2, ERK5 and expression of Bim were detected by Western blotting. Results: The results showed that HepG2/ADM and SMMC7721/ADM cells were resistant not only to ADM, but also to multiple anticancer drugs. When used alone, EGF had no anti-tumor activity in HepG2/ADM and SMMC7721/ADM cells in vitro, while it increased the cytotoxicity of ADM. EGF induced cell apoptosis and G0/G1 phase cell cycle arrest in HepG2/ADM And SMMC7721/ADM cells, while enhancing activity of p-ERKs and up-regulated expression of BimEL. Conclusions: EGF might enhance the chemosensitivity of HepG2/ADM and SMMC7721/ADM cells via up-regulating p-ERKs and BimEL protein.

• Biomolecules & Therapeutics
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• 제21권3호
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• pp.190-195
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• 2013

Cisplatin is a member of platinum-containing anti-cancer drugs that causes cross-linking of DNA and ultimately cancer cell apoptosis. The therapeutic function of cisplatin on various types of cancers has been widely reported but the side effects have been discovered together and nephrotoxicity has been regarded as major side effect of cisplatin. To select candidates for new sensitive nephrotoxicity biomarker, we performed proteomic analysis using 2-DE/MALDI-TOF-MS followed by cisplatin treatment in human kidney cell line, HK-2 cells, and compared the results to the gene profile from microarray composed of genes changed in expression by cisplatin from formerly reported article. Annexin A5 has been selected to be the most potential candidate and it has been identified using Western blot, RT-PCR and cell viability assay whether annexin A5 is available to be a sensitive nephrotoxic biomarker. Treatment with cisplatin on HK-2 cells caused the increase of annexin A5 expression in protein and mRNA levels. Over-expression of annexin A5 blocked HK-2 cell proliferation, indicating correlation between annexin A5 and renal cell toxicity. Taken together, these results suggest the possibility of annexin A5 as a new biomarker for cisplatin-mediated nephrotoxicity.

• Korean Journal of Acupuncture
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• 제22권3호
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• pp.165-174
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• 2005

Objective : The objective of this study is to investigate the inhibitor effects of an traditional oriental herb, Sophora flavescens on the hepatic and renal side effects of chemotherapy by using B16-BL6 melanoma-injected C57BL6 mouse tumor model. Methods : In this study, the effects of an traditional oriental herb, Sophora flavescens, on the side effects of chemotherapy were studied using B16 melanoma-injected C57BL6 mouse tumor model. Results : Sophora flavescen has significant effect on the reduction of the side effects of chemotherapy. Sophora flavescen recovered the reduction of WBC and RBC during cisplatin chemotherapy. Water extract of Sophora flavescens significantly inhibited cisplatin-induced increase of serum blood urea nitrogen (BUN) which is a good indicator of renal toxicity. Sophora flavescens extract does not decrease the anti-tumor activity of cisplatin showing that it can selectively inhibit side effects of anticancer drugs preserving beneficial effort. Conclusion : Theses results suggest a possibility that Sophora flavescens extract can be used for cancer patients for the reduction of the side effects and improving the quality of life during chemotherapy of cancer patients.

• Molecules and Cells
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• 제26권1호
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• pp.93-99
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• 2008

Transcriptional silencing is regulated by promoter methylation and histone modifications such as methylation and acetylation. We constructed a Schizosaccaromyces pombe reporter strain, KCT120a, to identify modifiers of transcriptional silencing, by inserting the $ura4^+$ gene into a heterochromatic telomere region. Two compounds inhibited the activity of histone deacetylases, induced acetylation of histone H3 and caused apoptotic cell death in HeLa cells. Expression of gelsolin and $p21^{waf1/cip1}$ also increased, as it does in response to HDAC inhibitors such as TSA. Therefore, these compounds appear to be potent inhibitors of HDACs, and hence potential anti-cancer drugs. Our observations suggest that a yeast cell-based assay system for transcriptional silencing may be useful for identifying histone deacetylase inhibitors and other agents affecting chromatin remodeling.

• The Korean Journal of Physiology and Pharmacology
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• 제3권1호
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• pp.75-82
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• 1999

It has been reported that activation of sphingomyelin pathway and nonsteroidal anti-inflammatory drugs (NSAIDS) inhibit the promotion of colon carcinoma. Ceramide, a metabolite of sphingomyelin, and indomethacin were shown to induce apoptosis in colon carcinoma cells. However, the mechanisms of ceramide- and indomethacin-induced apoptosis in the colon carcinoma cells are not clearly elucidated. Recent studys showed that indomethacin-induced apoptosis in colon cancer cells through the cyclooxygenase-independent pathways, and that may be mediated by generation of ceramide. In this study, we compared effects of ceramide and indomethacin on important modulators of apoptotic processes in HT29 cells, a human colon cancer cell line. Ceramide and indomethacin induced apoptosis dose- and time- dependently. Ceramide and indomethacin increased stress-activated protein kinase (SAPK) activity, and decreased mitogen-activated protein kinase (MAPK) activity. The expression of Bak was increased by the treatment of ceramide and indomethacin. The expression of other Bcl-2 related proteins (Mcl-1, $Bcl-X_L,$ Bax) which were known to be expressed in colon epithelial cells was not changed during the ceramide- and indomethacin-induced apoptosis. Our results suggest that ceramide and indomethacin share common mechanisms for induction of apoptosis in HT29 cells.

• Tuberculosis and Respiratory Diseases
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• 제56권2호
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• pp.169-177
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• 2004

연구배경 : Cyclooxygenase는 비스테로이드성 항염증제의 주요 작용부위로 실험적 모델이나 역학적 연구에서 암 발생을 억제하는 것으로 알려져 있다. COX-2는 prostaglandin E2와 같은 prostaglandin 합성을 통해 종양의 성장, 침윤 그리고 신생혈관에 중요한 역할을 하는 것으로 알려져 있다. 본 연구에서는 절제된 비소세포폐암조직에서 COX-2의 발현과 COX-2의 예후인자로서의 의의를 조사해 보았다. 대상 및 방법 : 1997년부터 2002년까지 본원에 내원하여 원발성 비소세포폐암으로 진단 받은 후 근치 목적의 절제술을 받았던 환자 84명을 대상으로 파라핀 포매된 조직을 택하여 면역 화학염색 방법을 통하여 COX-2 의 발현을 관찰하였다. COX-2가 발현된 암세포의 비율이 10% 이상인 경우를 양성으로 하였다. 결 과 : 평균 연령은 63세, 남녀 비는 67:17이었으며, 조직병리학적 분류는 편평상피암 53례, 선암 24례, 대세포암 7례였다. 병기는 I 병기 37례, II 병기 29례, IIIA 병기 18례였다. 총 84례 중 COX-2는 양성군이 73%(61/84례), 음성군이 27%(23/84례)이었다. COX-2 발현과 TNM 병기, 조직학적 분류와는 유의한 상관관계가 없었으나, 중간 생존기간은 COX-2 양성군이 음성군보다 통계적으로 유의하게 짧았다. 결 론 : 비소세포폐암에서 COX-2 항원 발현 음성군이 중간 생존기간이 길었다.