• 한국독성학회:학술대회논문집
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• 한국독성학회 2001년도 International Symposium on Dietary and Medicinal Antimutgens and Anticarcinogens
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• pp.170-170
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• 2001

This study was designed to evaluate a repeated intravenous dose toxicity of a new anticancer agent, SB extracted from Pulsatilla korean Nakai in Beagle dogs. Animals were intravenously injected with dosages of 0, 0.062, 0.25, and 1 mg/kg of SB everyday for 13 weeks, respectively. There were no dose-related changes in clinical signs, body weight changes, food and water consumptions, opthalmoscopy, and urine analysis. There were somewhat significant differences compared with control group in organ weight, biochemical examination, and hematology findings of animals treated with SB. However, these changes were not dose-related changes. Gross and histopathological findings revealed no evidence of specific toxicity related to SB. These indicate that intraveous maximum tolerated dose value of SB may be over 1mg/kg in rats.

• 생명과학회지
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• 제8권2호
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• pp.158-161
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• 1998

Farmesy-Protein Transferase의 저해제는 Ras단백질의 발암활성을 차잔하는 항암제의 후보로서 알려져있다. 우리는 최근에 topoisomerase I에 대하여 저해활성을 갖는 dihydrotanshinone I을 약용식물인 Salvia miltorhiza Bunge(Danshen)으로부터 분리하였다. Dihydrotanshinone Iml 작용기작의 해석을 위한 시도에서 farmesy-Protein Transferase에 대한 저해능($IC_{50}$치= 15ug/ml)을 관찰하였으며, 이것은 유용한 항암제로서의 가능성을 제시한 결과로 본다.

• Mycobiology
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• 제44권2호
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• pp.105-111
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• 2016

Paclitaxel (taxol) has long been used as a potent anticancer agent for the treatment of many cancers. Ever since the fungal species Taxomyces andreanae was first shown to produce taxol in 1993, many endophytic fungal species have been recognized as taxol accumulators. In this study, we analyzed the taxol-producing capacity of different Colletotrichum spp. to determine the distribution of a taxol biosynthetic gene within this genus. Distribution of the taxadiene synthase (TS) gene, which cyclizes geranylgeranyl diphosphate to produce taxadiene, was analyzed in 12 Colletotrichum spp., of which 8 were found to contain the unique skeletal core structure of paclitaxel. However, distribution of the gene was not limited to closely related species. The production of taxol by Colletotrichum dematium, which causes pepper anthracnose, depended on the method in which the fungus was stored, with the highest production being in samples stored under mineral oil. Based on its distribution among Colletotrichum spp., the TS gene was either integrated into or deleted from the bacterial genome in a species-specific manner. In addition to their taxol-producing capacity, the simple genome structure and easy gene manipulation of these endophytic fungal species make them valuable resources for identifying genes in the taxol biosynthetic pathway.

• Archives of Pharmacal Research
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• 제19권5호
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• pp.342-347
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• 1996

Doxorubicin, one of the clinically most useful anticancer agents, is used alone or in combination with other drugs against a wide variety of tumors, recently. But cancer cells developed resistance to this agent in many ways. This resistance is an important limiting factor of doxorubicin for anticancer drug. We newly established doxorubicin-resistant HCT15/CL02 subline from parental HCT15 human adenocarcinoma colon cancer cells. HCT15/CL02 revealed resistance to doxorubicin about 85-fold of its parental cells, and it also revealed cross-resistance to actinomycin D, etoposide and vinblastine but not to displatin and tamoxifen. And verapamil, a reversal agent of multidrug-resistance (MDR) by P-glycoprotein, elevated the cytotoxicity of doxorubicin against both HCT15 and GCT15/CL02 cells. But the relative resistant rate was not reduced. Verapamil had no effects on the tosicity of cisplatin to the both cell lines. These results indicate that HCT15/CL02 cells have some functionally complex mechanisms for MDR.

• 대한화학회지
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• 제37권1호
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• pp.136-140
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• 1993

새로운 methotrexate 중간체인 diethyl N-[4-{[(2,4-diamino-6-yl)methyl]-amino}benzoyl]-L-glutamate(10)를 합성하기 위하여 p-nitrobenzoic acid를 chlorination한 다음 L-glutamic acid와 coupling하고 이를 esterification한 후, 환원과 methylation시켜 diethyl N-(4-methylaminobenzoyl)-L-glutamate(7)를 합성하였다. 이 화합물(7)을 DMF 존재하에서 NaH와 allyl chloride를 가하여 allylation한 다음 여기에 $IN_3$ addition 반응으로 diethyl-p-[N-(2-azido-3-iodopropyl)-N-methyl]aminobenzoyl-L-glutamate(9)를 합성하였다. 이 화합물(9)을 2,4,5,6-tetraaminopyrimidine hydrochloride와 cyclization시켜 methotrexate diethylester를 얻었다.

• 대한수의학회지
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• 제61권3호
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• pp.22.1-22.7
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• 2021

Fenbendazole (FBZ) is a commonly used anthelmintics in veterinary medicine that has recently been found to have anticancer effects in humans. On the other hand, few studies have examined the anti-inflammatory effects of FBZ, and its mechanism is unknown. In this study, mouse bone marrow cells (BMs) were treated with lipopolysaccharide (LPS), a representative inflammation-inducing substance, to generate a situation similar to osteomyelitis in vitro. The effect of FBZ on inflammatory BMs was examined by measuring the metabolic activity, surface marker expression, cell nuclear morphology, and mitochondrial membrane potential (MMP) of BMs. FBZ decreased the metabolic activity and MMP of LPS-treated BMs. Annexin V-fluorescein isothiocyanate/propidium iodide staining and Hoechst 33342 staining showed that FBZ reduced the number of viable cells and induced the cell death of inflammatory BMs. In addition, FBZ reduced the proportion of granulocytes more than B lymphocytes in LPS-treated BMs. Overall, FBZ induces cell death by destabilizing the MMP of LPS-induced inflammatory BMs. In addition to anthelmintic and anticancer agent, FBZ can play a role as an anti-inflammatory agent.

• Asian Pacific Journal of Cancer Prevention
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• 제16권15호
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• pp.6513-6519
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• 2015

Background: Recent attention on chemotherapeutic intervention against cancer has been focused on discovering and developing phytochemicals as anticancer agents with improved efficacy, low drug resistance and toxicity, low cost and limited adverse side effects. In this study, we investigated the effects of Curcuma C20-dialdehyde on growth, apoptosis and cell cycle arrest in colon and cervical cancer cell lines. Materials and Methods: Antiproliferative, apoptosis induction, and cell cycle arrest activities of Curcuma C20-dialdehyde were determined by WST cell proliferation assay, flow cytometric Alexa fluor 488-annexin V/propidium iodide (PI) staining and PI staining, respectively. Results: Curcuma C20 dialdehyde suppressed the proliferation of HCT116, HT29 and HeLa cells, with IC50 values of $65.4{\pm}1.74{\mu}g/ml$, $58.4{\pm}5.20{\mu}g/ml$ and $72.0{\pm}0.03{\mu}g/ml$, respectively, with 72 h exposure. Flow cytometric analysis revealed that percentages of early apoptotic cells increased in a dose-dependent manner upon exposure to Curcuma C20-dialdehyde. Furthermore, exposure to lower concentrations of this compound significantly induced cell cycle arrest at G1 phase for both HCT116 and HT29 cells, while higher concentrations increased sub-G1 populations. However, the concentrations used in this study could not induce cell cycle arrest but rather induced apoptotic cell death in HeLa cells. Conclusions: Our findings suggest that the phytochemical Curcuma C20-dialdehyde may be a potential antineoplastic agent for colon and cervical cancer chemotherapy and/or chemoprevention. Further studies are needed to characterize the drug target or mode of action of the Curcuma C20-dialdehyde as an anticancer agent.

• Asian Pacific Journal of Cancer Prevention
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• 제15권18호
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• pp.7785-7792
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• 2014

Background: Valproic acid (VPA) is a potent anticancer and antiangiogenic agent. However, design and synthesis of chemical derivatives with improved antiangiogenic and anticancer activities are still necessary. In this study a library of novel derivatives of VPA was synthesized and tested. Methods: A human liver cancer cell line (HepG2) and a human normal embryonic kidney cell line (HEK 293) were exposed to various concentrations of VPA derivatives for 24 hours and cell viability was checked by MTT colorimetric assay. Anti-angiogenic properties were evaluated in transgenic zebrafish embryos. Results: N-valproylglycine derivatives suppressed survival almost 70% (p value 0.001) in HepG2 cells but only 10-12% in HEK 293 cells (p value 0.133). They also suppressed angiogenic blood vessel formation by 80% when used between $2-20{\mu}M$ in zebrafish embryos. Valproic acid hydrazides showed moderate level of anticancer activity by affecting 30-50% (p value 0.001) of cell viability in HepG2 cells and 8-10% in HEK293 cells (p value 0.034). Conclusion: The majority of compounds in this study showed potent and stronger antiangiogenic and anticancer activity than VPA. They proved selectively toxic to cancer cells and safer for normal cells. Moreover, these compounds inhibited developmental angiogenesis in zebrafish embryos. Based on the fact that liver is a highly vascularized organ, in case of liver carcinoma these compounds have the potential to target the pathological angiogenesis and could be an effective strategy to treat hepatocellular carcinoma.

• Asian Pacific Journal of Cancer Prevention
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• 제15권15호
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• pp.6437-6441
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• 2014

Background: Oridonin isolated from Rabdosia rubescens, a plant used to treat cancer in Chinese folk medicine, is one of the most important antitumor active ingredients. Previous studies have shown that oridonin has antitumor activities in vivo and in vitro, but little is known about cell cycle effects of oridonin in gastric cancer. Materials and Methods: MTT assay was adopted to detect the proliferation inhibition of SGC-7901 cells, the cell cycle was assessed by flow cytometry and protein expression by Western blotting. Results: Oridonin could inhibit SGC-7901 cell proliferation, the $IC_{50}$ being $15.6{\mu}M$, and blocked SGC-7901 cell cycling in the $G_2/M$ phase. The agent also decreased the protein expression of cyclinB1 and CDK1. Conclusions: Oridonin may inhibit SGC-7901 growth and block the cells in the $G_2/M$ phase by decreasing Cdk1 and cyclinB1 proteins.

• The Korean Journal of Physiology and Pharmacology
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• 제27권1호
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• pp.31-38
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• 2023

Carboplatin, an advanced anticancer drug with excellent efficacy against ovarian cancer, was developed to alleviate the side effects that often occur with cisplatin and other platinum-based compounds. Our study reports the in vitro characteristics, viability, and activity of cells expressing the inducible nitric oxide synthase (iNOS) gene after carboplatin was conjugated with polysuccinimide (PSI) and administered in combination with other widely used anticancer drugs. PSI, which has promising properties as a drug delivery material, could provide a platform for prolonging carboplatin release, regulating its dosage, and improving its side effects. The iNOS gene has been shown to play an important role in both cancer cell survival and inhibition. Herein, we synthesized a PSI-carboplatin conjugate to create a modified anticancer agent and confirmed its successful conjugation. To ensure its solubility in water, we further modified the structure of the PSI-carboplatin conjugate with 2-aminoethanol groups. To validate its biological characteristics, the ovarian cancer cell line SKOV-3 and normal ovarian Chinese hamster ovary cells were treated with the PSI-carboplatin conjugate alone and in combination with paclitaxel and topotecan, both of which are used in conventional chemotherapy. Notably, PSI-carboplatin conjugation can be used to predict changes in the genes involved in cancer growth and inhibition. In conclusion, combination treatment with the newly synthesized polymer-carboplatin conjugate and paclitaxel displayed anticancer activity against ovarian cancer cells but was not toxic to normal ovarian cancer cells, resulting in the development of an effective candidate anticancer drug without severe side effects.