• 약학회지
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• 제49권1호
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• pp.38-43
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• 2005

The occurrence of resistance to chemotherapeutic drugs is a major problem for successful cancer treatment. This resistant phenotype of cancer cell frequently reveals a broad spectrum to structurally and/or functionally unrelated anticancer drugs, termed multidrug resistance (MDR). Overexpression of P-glycoprotein (P-gp), a transmembrane drug efflux pump, is a major mechanism of MDR. Accordingly, considerable effort has been directed towards to development of compounds that inhibit P-gp, reverse the MDR phenotype and sensitize cancer cells to conventional chemotherapy without undesired toxicological effects. In an effort to search for novel MDR reversal agent, we tested the cytotoxicity of paclitaxel, a well-known substrate of P-gp, against P-gp-expressing HCT15 and HCT15/CL02 human colorectal cancer cells in the presence or absence of benzotriazepin analogues, as well as against P-gp-negative A549 human non-small cell lung and SK-OV-3 human ovarian cancer cells in vitro. Among the compounds tested, the agents that have phenyl amide moiety at 3 position remarkably increased the cytotoxicity of paclitaxel against P-gp-expressing cancer cells, but not against P-gp-negative cancer cells. BTZ-15 and BTZ-16 at $4\;{\mu}M$ revealed similar MDR reversal activity to $10\;{\mu}M$ verapamil, a well-known MDR reversal agent.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제28권2호
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• pp.95-110
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• 2006

The treatment for oral and maxillofacial carcinoma with chemotherapeutic agents is evaluated by many effective methods to reduce the tumor mass and cancer cell proliferation. However these chemotherapy have many serious side effects, such as bone marrow suppression, renal toxicity, G-I troubles. Therefore a possible approach to develop a clinically applicable chemotherapeutic agent is to screen anticancer activity of Taxol which is known to have very little side effect and have been used to breast cancer and ovarian carcinoma. Taxol is a new anti-microtubular anti-cancer agent extracted from the bark of the Pacific yew, Taxus brevifolia. Paclitaxel(Taxol) acts by promoting tubulin polymerization and over stabilizing microtubules agianst depolymerization. Despite the constant improvements of methods of the cancer treatment especially chemotherapy, the rate of cancer metastasis and recurrent are not decreased. Thus the investigation of new drug which have very little side effect and a possible clinically application continues to be a high priority. Considering that the Taxol have shown very effective chemotherapeutic agent with relatively low toxicity in many solid tumors, it deserves to evaluate its efficacy in oral squamous cell carcinoma. In this study, to investigate the in-vivo and in-vitro anti-cancer efficacy of Taxol in oral squamous cell carcinoma and lastly, the potency of Paclitaxel in the clinical application for oral cancer was evaluated. In vivo study, after HN22 cell line were xenografted in nude mice, the growth of tumor mass was observed, 3 mg/Kg taxol was injected intraperitoneally into nude mice containing tumor mass. The methods of these study were measurement of total volume of tumor mass, histopathologic study, immunohistochemical study, drug resistance assay, growth curve, MTT assay, flow cytometry, cDNA microarray in vivo and in vitro. The results were obtained as following. 1. The visual inspection of the experimental group showed that the volume of the tumor mass was slightly decreased but no significant difference with control group. 2. Ki-67 index was decreased at weeks 4 in experimental group. 3. Microscopic view of the xenografted tumor mass showed well differentiated squamous cell carcinoma and after Taxol injection, some necrotic tissue was seen weeks 4. 4. The growth curve of the tumor cells were decreased after 1day Taxol treatment. 5. According to the MTT assay, HN22 cell line showed relative drug resistancy above $5\;{\mu}g/ml$ concentrations of Taxol. 6. In drug resistance assay, the decrease of cell counts was seen relatively according to concentration. 7. In Flow cytometry, G2M phase cell arrests were seen in low concentration of the Taxol, while S phase cell arrests were seen in high concentration of the Taxol. 8. Using cDNA microarray technique, variable gene expression of ANGPTL4, TXNRD1, FAS, RRAGA, CTGF, CYCLINEA, P19, DUSP5, CEBPG, BTG1 were detacted in the oral squamous cell carcinoma cell after taxol treatment. In this study paclitaxel is effective against oral squamous cell carcinoma cell lines in vitro, but week effect was observed in vivo. So we need continuous study about anticancer effect of taxol in vivo in oral squamous cell carcinoma.

• 생명과학회지
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• 제25권9호
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• pp.1051-1058
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• 2015

본 연구에 평가된 감귤 돌연변이는 기존 궁천조생 품종에서 유래된 방사선 돌연변이체로 선행 연구에서 다양한 생리활성 및 기능성 성분이 함유되어 있다는 것을 보고한 이래로, 감귤 돌연변이의 항암 제제로써 활용 가능성을 검증하였다. 여러 암종(HCT116, 인간대장암세포; A375, 인간흑색종세포; Hela, 인간자궁경부암세포; MCF-7, 인간유방암세포; A549, 인간폐암세포; HepG2, 인간간암세포)을 대상으로 감귤 돌연변이의 항암 활성을 기존 궁천조생 품종(방사선 무처치군)과 비교 분석한 결과 그 효용 가치가 높게 나타났을 뿐 아니라 자연사멸 유도 메커니즘을 탐색하였을 때 감귤 돌연변이에 의해 야기된 apoptosis에 IAP family의 발현 저해와 NO^• pathway 증강에 따라 세포 고사가 촉진됨을 확인할 수 있었다. 또한 감귤 돌연변이가 정상 세포에 대한 독성을 유발하지 않는 것으로 나타나, 암세포 선택성이 높은 chemopreventive 및 chemotherapeutic agent로 개발 가능할 것으로 예상되며 이를 위해 향후 보다 정밀한 자연사멸의 분자생물학적 기전 규명이 수반되어야 할 것으로 사료된다.

• 생명과학회지
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• 제21권8호
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• pp.1109-1119
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• 2011

예로부터 한국, 일본 및 중국에서 민간처방 약재 및 건강식품으로 사용되어온 매실은 다양한 효능을 가지는 것으로 알려져 있으나 인체 암세포에서 유발하는 항암작용 및 그에 따른 분자생물학적 기작에 대해서는 명확히 밝혀져 있지 않다. 본 연구에서는 인체 혈구암 U937 세포에서 매실의 메탄올 추출물(MEPM)이 유발하는 항암효과 및 항암기전을 조사한 결과, MEPM 처리 농도 의존적으로 암세포의 성장억제 및 apoptosis를 유발하는 것으로 나타났다. MEPM에 의해서 유발되는 apoptosis에는 XIAP 및 survivin 등과 같은 IAP family의 발현 감소와 더불어 FasL의 발현 증가, Bcl-2의 발현 감소 및 Bid의 단편화 현상이 관여하는 것으로 나타났으며, 두 가지 apoptosis 유발 개시 및 최종 apoptosis 단계에서 중요한 역할을 하는 caspase-8과 -9 및 -3의 활성화와 그에 따른 다양한 기질단백질의 발현 감소 및 단편화가 동반되었음을 알 수 있었다. 또한 인위적인 caspase-3의 활성 차단으로 MEPM에 의하여 유발되는 apoptosis가 현저하게 억제되는 것으로 나타났다. 이상의 결과에서 MEPM은 암세포의 chemotherapeutic agent로서의 가능성을 확인하였지만 향후 지속적인 연구를 통하여 활성물질의 동정 및 관련 기전의 비교 등이 지속적으로 이루어져야 할 것으로 생각된다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권24호
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• pp.10949-10955
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• 2015

Liver cancer is one of leading digestive malignancies with high morbidity and mortality. There is an urgent need for the development of novel therapies for this deadly disease. It has been proven that asparagus polysaccharide, one of the most active derivates from the traditional medicine asparagus, possesses notable antitumor properties. However, little is known about the efficacy of asparagus polysaccharide as an adjuvant for liver cancer chemotherapy. Herein, we reported that asparagus polysaccharide and its embolic agent form, asparagus gum, significantly inhibited liver tumor growth with transcatheter arterial chemoembolization (TACE) therapy in an orthotopic hepatocellular carcinoma (HCC) tumor model, while significantly inhibiting angiogenesis and promoting tumor cell apoptosis. Moreover, asparagine gelatinous possessed immunomodulatory functions and showed little toxicity to the host. These results highlight the chemotherapeutic potential of asparagus polysaccharide and warrant a future focus on development as novel chemotherapeutic agent for liver cancer TACE therapy.

• 대한약리학회지
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• 제32권1호
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• pp.93-102
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• 1996

일부 malignant tumor에 Pt-complex의 임상 응용 과정에서 신장독성등의 심한 부작용이 문제점으로 지적되고 있다. 이 연구에서는 기존의 cisplatin보다 항암효과는 우수하면서, 부작용을 감소시킨 새로운 Pt complex의 개발에 역점을 두었다. 본 연구에서 합성한 Pt(II) complex는 carrier ligand로서 1,2-diaminocyclohexane(dach)을 사용하였고, leaving group으로는 diphosphine류인 1,3-bis (diphenylphosphine의 propane(DPPP) 을 도입하였으며, 물에 대한 용해도를 높이기 위해 dinitrate로 만들었다. 새로이 합성한 [Pt(II)(cia-dach)(DPPP)].$(NO_3)_2$ 은 원소 분석, IR 및 $^{13}C-NMR$ 분석 data에 의하여 위의 물질임이 확인되었다. PC-1은 MTT assay method에 의한 항암활성 연구를 통하여 SKOV-3, OVCAR-3 human ovarian adenocarcinoma cells에서 항암효과가 인정되었으며, 이 항암효과는 대조 약물로 사용된 cisplatin과 유사하였다. PC-1은 토끼의 신세뇨관 세포와 인체의 신피질 세포를 이용한 cytotoxity 및 thymidine 섭취율과 인체 신피질 조직 배양을 이용한 glucose consumption 실험을 통하여 모두 cisplatin보다 신장독성이 현저히 감소되었다. 이상의 결과로 보아 Pt(II) complex는 carrier ligand와 leaving group의 선택에 따라 항암활성의 증가와 신독성의 감소를 일으키는 요인으로 보여지며, 이 연구에서 만들어진 새로운 Pt(II) complex는 앞으로 다각적인 검토를 거쳐 새로운 anticancer chemotherapeutic agent로 개발될 가능성이 있을 것으로 생각된다.

• Asian Pacific Journal of Cancer Prevention
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• 제14권4호
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• pp.2503-2508
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• 2013

Histone deacetylation mediated by histone deacetylases (HDACs) has been reported as one of the epigenetic mechanisms associated with tumorigenesis. The poor responsiveness of anticancer drugs found with cholangiocarcinoma (CCA) leads to short survival rate. We aimed to investigate mRNA expression of HDACs class I and II, and the effect of HDAC inhibitors, suberoylanilide hydroxamic acid (SAHA) and valproic acid (VPA), in CCA in vitro. Expression of HDACs was studied in CCA cell lines (M213, M214 and KKU-100) and an immortal cholangiocyte (MMNK1) by semi-quantitative reverse transcription-PCR. SAHA and VPA, as well as a classical chemotherapeutic drug 5 -fluorouacil (5-FU) were used in this study. Cell proliferation was determined by sulforhodamine assay. $IC_{50}$ and $IC_{20}$ were then analyzed for each agent and cell line. Moreover, synergistic potentional of VPA or SAHA in combination with 5-FU at sub toxic does ($IC_{20}$) of each agent was also evaluated. Statistic difference of HDACs expression or cell proliferation in each experimental condition was analyzed by Student's t-test. The result demonstrated that HDACs were expressed in all studied cell types. Both SAHA and VPA inhibited cell proliferation in a dose-dependent manner. Interestingly, KKU-100 which was less senstitive to classical chemotheraoeutic 5-FU was highly was sensitive to HDAC inhibitors. Simultaneous combination of subtoxic doses of HDAC inhibitors and 5-FU signiicantly inhibited cell proliferation in CCA cell lines compared to single sgent treatment($P{\leq}0.01$), while sequentially combined treatments were less effective. The present study showed inhibitory effects of HDACIs on cell proliferation in CCA cell lines, with synergistic antitumor potential demonstrated by simultaneous combination of VPA or SAHA with 5-FU, suggesting a novel alternative therapeutic strategy in effective treatment of CCA.

• Asian Pacific Journal of Cancer Prevention
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• 제17권5호
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• pp.2683-2688
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• 2016

A salt compound of a curcumin analogue, potassium pentagamavunon-0 (K PGV-0) has been synthesized to improve solubility of pentagamavunon-0 which has been proven to have anti-proliferative effects on several cancer cells. The purpose of this study was to investigate cytotoxic activity and metastasis inhibition by K PGV-0 alone and in combination with achemotherapeutic agent, doxorubicin (dox), in breast cancer cells. Based on MTT assay analysis, K PGV-0 showed cytotoxic activity in T47D and 4T1 cell lines with $IC_{50}$ values of $94.9{\mu}M$ and $49.0{\pm}0.2{\mu}M$, respectively. In general, K PGV-0+dox demonstrated synergistic effects and decreased cell viability up to 84.7% in T47D cells and 62.6% in 4T1 cells. Cell cycle modulation and apoptosis induction were examined by flow cytometry. K PGV-0 and K PGV-0+dox caused cell accumulation in G2/M phase and apoptosis induction. Regarding cancer metastasis, while K PGV-0 alone did not show any inhibition of 4T1 cell migration, K PGV-0+dox exerted inhibition. K PGV-0 and its combination with dox inhibited the activity of MMP-9 which has a pivotal role in extracellular matrix degradation. These results show that a combination of K PGV-0 and doxorubicin inhibits cancer cell growth through cell cycling, apoptosis induction, and inhibition of cell migration and MMP-9 activity. Therefore, K PGV-0 may have potential for development as a co-chemotherapeutic agent.

• 대한미생물학회지
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• 제15권1호
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• pp.33-38
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• 1980

Shigella remains to be an important enteric pathogen in this country for the moment. Moreover, since 1978, most of the isolates have become resistant to ampicillin and co-trimoxazole, which used to be the drugs of choice for shigellosis. Since a disc diffusion technique alone has been used in our routine susceptibility test, the minimum inhibitory concentrations(MIC) of both ampicillin and co-trimoxazole to Shigella have never been known. In order to determine these, 195 isolates were tested by an agar dilution method, all of which were isolated at Yonsei Medical Center during the period of June 1978 to July 1980. The following results were obtained. 1. Sixty cultures(29.7%) were susceptible to ampicillin, being the MIC of 8 ${\mu}g/ml$ or less and 53(27.2%) were susceptible to co-trimoxazole, being the MIC of TMP/SMZ 4/76 ${\mu}g/ml$ or less. S. flexneri type 2 was often resistant to both antimicrobic agents. 2. An increasing rate of resistant isolates was noted, particularly in the year of 1979. 3. Many isolates were resistant to both agents. Somewhat more cultures. were ampicillin susceptible and co-trimoxazole resistant than the other way around. It seems that the determination of species or even serotypes might be of help sometimes to select proper antimicrobic agent to control the infection. A routine antimicrobic susceptibility test of Shigella to both ampicillin and co-trimoxazole would be advisable for a better selection of chemotherapeutic agent.

• Asian Pacific Journal of Cancer Prevention
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• 제15권21호
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• pp.9049-9058
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• 2014

Casticin (3', 5-dihydroxy-3, 4', 6, 7-tetramethoxyflavone) is an active compound isolated from roots, stems, leaves, fruits and seeds of a variety of plants. It is well known for its pharmacological properties and has been utilized as an anti-hyperprolactinemia, anti-tumor, anti-inflammatory, neuroprotetective, analgesic and immunomodulatory agent. Recently, the anticancer activity of casticin has been extensively investigated. The resulkts showed that it exerts protective potential by targeting apoptosis, considered important for cancer therapies. In this article, our aim was to review the pharmacological and therapeutic applications of casticin with specific emphasis on its anticancer functions and related molecular mechanisms. Chemotherapeutic effects are dependent on multiple molecular pathways, which may provide a new perspective of casticin as a candidate anti-neoplastic drug. This review suggests that additional studies and preclinical trials are required to determine specific intracellular sites of action and derivative targets in order to fully understand the mechanisms of its antitumor activity and validate this compound as a medicinal agent for the prevention and treatment of various cancers.