• Archives of Pharmacal Research
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• 제18권2호
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• pp.138-139
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• 1995

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.181.2-181.2
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• 2003

Inosine monophosphate dehydrogenase(IMPDH) catalyzes the $NAD^+$-dependent oxidation of IMP to XMP, the rate limiting step in the de novo biosynthesis of guanine nucleotide. Its critical role at the metabolic branch point in purine nucleotide biosynthesis makes it a useful target in the development of drugs for antiviral and anticancer chemotherapy and in immunosupressant area. Several compound with antiviral activity have been found to be inhibitors of IMPDH. For example, ribavirin, a competitive inhibitor of IMPDH, has broad spectrum antiviral activities against DNA and RNA viruses. (omitted)

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1994년도 제2회 추계심포지움
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• pp.147-172
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• 1994

Aziridinylbenzoquinones such as 3, 6-diaziridinyl-1, 4-benzoquinone (DZQ) and its 2, 5-methyl analog (MeDZQ) require bioreductive activation in order to elicit their anticancer activities. To determine the involvement of DTD in the activation of these drugs, we have used a ligation-mediated polymerase chain reaction to map the intracellular alkylation sites in a sing1e copy gene at the nucleotide level. We have performed this analysis in two human colon carcinoma cells, one proficient (HT-29) and one deficient (BE) in DT-diaphorase (DTD) activity. In the DTD proficient HT-29 cell line, DZQ and MeDZQ were found to alkylate both 5'-(A/T)G(C)-3' and 5'-(A/T)A-3' sequences. This is consistent with the nucleotide preferences observed when DZQ and MeDZQ are activated by purified DTD to reactive metabolites capable of alkylating DNA in vitro [Lee, C. -S., Hartley, J. A., Berardini, M. D., Butler, J., Siegel., D., Ross, D., & Gibson, N. W. (1992) Biochemistry, 31: 3019-3025]. Surprisingly in the DTD-deficient BE cell line a pattern of alkylation induced by DZQ and MeDZQ similar to that observed in the DTD-proficient HT-29 cells was observed. This suggests that reductive enzymes other than DTD can be involved in activating DZQ and MeDZQ to DNA reactive species in vivo.

• 자연과학논문집
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• 제9권1호
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• pp.31-37
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• 1997

세포의 자살 현상은 항암제를 이용한 치료법에 있어 중요하다. p53 은 세포 자살을 유발하여 암세포를 죽이는 핵심적 요소임이 밝혀졌다. 그러나 최근의 연구는 p53 과 무관한 세포 자살 경로가 있음을 보였다 (Gaftenhaus 외, 1996). 본 저자들은 유전독성적 항암제인 아드리아마이신에 의하여 유도된 세포 자살 과정에서 p53 유전자의 돌연변이가 일어나는지를 관찰하였다. 그러므로 본 연구는 아드리아마이신에 의하여 유도된 세포 자살 과정에서 HeLa 세포 집단에서의 p53 유전자의 돌연변이 상태를 조사하였다. DNA 분절 현상으로 관찰한 바, 본 실험 조건하에서는 아드리아마이신을 1 uM 농도로 12 시간 처리하였을 때 세포 자살 현상이 일어났다. p53 유전자의 돌연 변이 상태를 관찰하고자 돌연변이 빈발 부위가 존재한다고 알려진 exon 5, 7 및 8 부위를 종합 효소연쇄반응으로 증폭변화는 관찰되지 않았다. 그러므로 본 연구는 p53 유전자 손상없이 아드리아마이신에 의하여 세포 자살이 유도됨을 밝혔다.

• Biomolecules & Therapeutics
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• 제3권2호
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• pp.97-103
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• 1995

The purpose of this study was to determine pharmacokinetic parameters of BR-28702-2, a new antineoplastic agent which is the conjugate of nucleotide and phospholipid, and to compare them with those of ara-C. Male rats were cannulated in the left femoral vein and received a single i.v. bolus dose of either BR-28702-2 or ara-C. BR-28702-2 was also administered i.p. and plasma samples were analyzed by reversedphase HPLC. The t$_{1}$2($\beta$)/ of ara-C(1.22 hr.) was significantly smaller than that of BR-28702-2(4.420 hr.). The absolute bioavailability of BR-28702-2 after i.p. injection was 1.125%. This lower bioavailability, together with previous reports that marked antineoplastic activity was observed when given i.p., indicates that BR-28702-2 would act as a depot system to release active moieties. Further works, therefore, need to be done to characterize active metabolites.

• 대한의생명과학회지
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• 제29권1호
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• pp.41-47
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• 2023

Discovery of new substance that can regulate platelet aggregation or suppress aggregation will aid in the prevention and treatment of cardiovascular diseases. Artesunate is a compound from plant roots of Artemisia or Scopolia, and its effects have shown to be promising in areas of anticancer and Alzheimer's disease. However, the role and mechanisms by which artesunate affects the aggregation of platelets, and the formation of a thrombus are currently not understood. This study examined the ways artesunate affects platelets activation and thrombus formation induced by collagen. As a result, cAMP and cGMP production were increased significantly by artesunate relative to the doses, as well as phosphorylated VASP and IP₃R, substrates to cAMP-dependent kinase and cGMP-dependent kinase, in a significant manner. The Ca²⁺ normally mobilized from the dense tubular system was inhibited due to IP₃R, phosphorylation from artesunate, and phosphorylated VASP aided in inhibiting platelet activity via αIIb/β₃ platelet membrane inactivation and inhibiting fibrinogen binding. Finally, artesunate inhibited thrombin-induced thrombus formation. Therefore, we suggest that artesunate has importance with cardiovascular diseases stemming from the abnormal platelets activation and thrombus formation by acting as an effective prophylactic and therapeutic agent.

• Molecular & Cellular Toxicology
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• 제2권2호
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• pp.141-149
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• 2006

Tamoxifen (TAM), a non-steroidal anti estrogen anticancer drug and chemopreventive agent for breast cancer, have caused cholestasis in liver. The potent hepatocarcinogenicity of this drug has been reported. Methotrexate (MTX) is dihydrofolate reductase inhibitor which interfaces with the synthesis for urine nucleotide and dTMP. And it may cause atrophy, necrosis and steatosis in liver. These two anticancer drug have well-known hepatotoxicity. So, in this study we compare the gene expression pattern of antitumor agent TAM and MTX, using the cDNA microarray. We have used 4.8 K cDNA microarray to identify hepatotoxicity-related genes in 5-week-old male Sprague-Dawley (SD) rats. Confirm the pattern of gene expression, we have used Real time PCR for targeted gene. In the case of MTX, Protease related gene (Ctse, Ctsk) and Protein kinase (Pctk 1) have shown specific expression pattern. And in the case of TAM, apoptosis related gene (Pdcd 8) and signal transduction related gene (kdr) have significantly up regulated during treatment time. Gene related with growth factor, lipid synthesis, chemokins were significantly changed. From the result of this study, the information about influence of TAM and MTX to hepatoxicity will provide.

• 한국버섯학회지
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• 제15권4호
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• pp.155-163
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• 2017

Mushrooms and their extracts including purified ingredients, are currently used as foods, functional foods (and/or nutraceuticals), and medicines. These products have numerous bioactive compounds such as polysaccharides (mainly ${\beta}$-glucans), glycoproteins, nucleotide analogs, terpenoids, and polyphenols, which have exhibited antioxidant, antimicrobial, anticancer, antiviral, anti-obesity, and immunomodulatory activities. In this review, we discuss the current information on the biactivities of 10 popular mushrooms in Korea. We also summarize the information on mushrooms and the active compounds derived from them, as well as mushroom-based products such as foods, functional foods, and medicines. We believe this review could provide useful information for scientists and consumers who seek to develop new products and promote healthy food habits and lifestyle.

• 대한수의학회지
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• 제43권2호
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• pp.211-218
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• 2003

Human ovarian cancerous cells survive in a way that they trigger the nucleotide excision repair (NER) or double-strand DNA repair (dsDNA) repair mechanism to show resistance to anticancer drugs and activate many kinds of repair protein, thus removing damaged DNAs. Two experiments on the PA-1 human ovarian teratocareinoma cell line that hardly has any expression of epidermal growth factor receptor (EGFR) were conducted in the study; first, EGF-R was transfected and its receptor was obtained. The receptor was investigated in terms of its mutual relations with many kinds of protein concerning NER or dsDNA repair. Second, it was examined what kind impact cisplatin and adriamycin had on the effects of EGF-R over the PA-1 cell line lacking EGF-R. When being administered with cisplatin and adriamycin, Hey and Hey C2 cell lines showed a high level of resistance while PA-1 cell line a high level of sensitivity. Hey and Hey C2 cell lines that are resistant against anticancer drugs exhibited a high level of EGF-R expression while PA-1 cell line that is sensitive to them did a much lower level of the expression. When PA-1 cell line was transfected for the expression of DNA adduct and EGF-R, it showed a higher level of resistance compared to the control group. There was no difference in the expression of DNA repair proteins (DNA- dependent protein kinase, Ku70, and Ku80) between Hey and the PA-1 cell lines. The results indicate that the Hey cell line that is resistant against cisplatin and adriamycin works along the signaling system responding to the changes of EGF-R while the PA-1 cell line that is sensitive to both of them does to the lack of EGF-R.

• Journal of Applied Biological Chemistry
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• 제63권3호
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• pp.235-241
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• 2020

An essential component of the hemostatic process during vascular damage is platelet activation. However, many cardiovascular diseases, such as atherosclerosis, thrombosis, and myocardial infarction, can develop due to excessive platelet activation. Isoscopoletin, found primarily in plant roots of the genus Artemisia or Scopolia, has been studied to demonstrate potential pharmacological effects on Alzheimer's disease and anticancer, but its mechanisms and role in relation to thrombus formation and platelet aggregation have not yet been discovered. This research investigated the effect of isoscopoletin on collagen-induced human platelet activation. As a result, isoscopoletin strongly increased cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) levels in a concentration-dependent manner. In addition, isoscopoletin greatly phosphorylated inositol 1,4,5-triphosphate receptor (IP₃R) and vasodilator-stimulated phosphoprotein (VASP), known substrates of cAMP-dependent kinase and cGMP dependent kinase. Phosphorylation of IP₃R by isoscopoletin induced Ca²⁺ inhibition from the dense tubular system Ca²⁺ channels, and VASP phosphorylation was involved in fibrinogen binding inhibition by inactivating αIIb/β₃ in the platelet membrane. Isoscopoletin finally reduced thrombin-induced fibrin clot production and finally reduced thrombus formation. Therefore, this research suggests that isoscopoletin has strong antiplatelet effects and is likely to be helpful for thrombotic diseases involving platelets by acting as a prophylactic and therapeutic agent.