• 생약학회지
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• 제45권1호
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• pp.1-10
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• 2014

Ginsenoside Rg3 (G-Rg3) is one of protopanaxadiol ginsenosides characteristic of red ginseng, steamed and dried ginseng (Panax ginseng), which has recently attracted much attention for its antitumor properties in vitro and in vivo animal models. Experimental studies have demonstrated that it could promote cancer cell apoptosis, inhibit cancer cell growth, the apoptosis of cancer cells, adhesion, invasion and metastasis, and also prevent an angiogenetic formation in prostate, breast, ovarian, colorectal, gastric, liver and lung cancer etc. It has shown the antitumor activities by modulation of diverse signaling pathways, including regulation of cell proliferation mediators (CDKs and cyclins), growth factors (vascular endothelial growth factor), tumor suppressors (p53 and p21), cell death mediators (caspases, Bcl-2, Bax), inflammatory response molecules ($NF-{\kappa}B$ and COX-2), protein kinases (JNK, Akt, and AMP-activated protein kinase) and Wnt/${\beta}$-catenin signaling. In addition, the combination of Rg3 and chemotherapeutic agents have synergistically enhanced therapeutic efficacy and reduced antagonistically side effects. Furthermore, it can reverse the multidrug resistance of cancer cells, prolong the survival duration and improve life quality of cancer patients. Taken together, accumulating evidences could provide the potential of G-Rg3 in the treatment of cancers and the feasibility of further randomized placebo controlled clinical trials.

• Archives of Pharmacal Research
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• 제29권12호
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• pp.1067-1073
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• 2006

Cisplatin, a platinum coordinated complex, is a widely used antineoplastic agent for the treatment of metastatic tumors of the testis, metastatic ovarian tumors, lung cancer, advanced bladder cancer and many other solid tumors. The cytotoxic action of the drug is often thought to be associated with its ability to bind DNA to form cisplatin-DNA adducts. The development of resistance to cisplatin during treatment is common and constitutes a major obstacle to the cure of sensitive tumors. Although to understand the clinically relevant mechanisms of resistance, many studies have been aimed at clarifying the biochemical/molecular alterations of cisplatin-resistance cells, these studies did not conclusively identify the basis of cellular resistance to cisplatin. In this review, cisplatin resistance was discussed in terms of the relevant transporters, such as copper transporters (CTRs), organic cation transporters (OCTs) and multi-drug resistance related transporters (MDRs). These transporters seem to be contributed to cisplatin resistance through the reduction of drug accumulation in the cell. Better understanding the mechanism of cisplatin resistance associated with transporters will provide the useful informations for overcoming the cisplatin resistance.

• 약학회지
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• 제52권1호
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• pp.67-72
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• 2008

The use of doxorubicin, which is one of the most effective anticancer agents, is often limited by occurrence of acquired resistance in tumor cells. GSH has been shown to be involved in the development of this drug resistance. Transcription factor Nrf2 governs the expression of GSH synthesizing glutamylcysteine ligase (GCL), as well as multiple phase 2 detoxifying enzymes. Here we show that Nrf2 is one of factors determining doxorubicin sensitivity. Nrf2-deficient fibroblasts (murine embryonic fibroblasts, MEF) were more susceptible to doxorubicin mediated cell death than wild-type cells. Doxorubicin treatment elevated levels of Nrf2-regulated genes including NAD(P)H: quinone oxidoreductase (Nqo1) and GCL in wild-type fibroblasts, while no induction was observed in Nrf2-deficient cells. Doxorubicin resistance in human ovarian SK-OV cells was reversed by treatment with L-buthionine-sulfoxamine (BSO), which is depleting intracellular GSH. Finally, transfection of SK-OV cells with Nrf2 siRNA resulted in exacerbated cytotoxicity following doxorubicin treatment compared to scrambled RNA control. These results indicate that the Nrf2 pathway, which plays a protective role in normal cells, can be a potential target to control cancer cell resistance to anticancer agents.

• Archives of Pharmacal Research
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• 제19권4호
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• pp.286-291
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• 1996

Phenolic compounds are prevalent as toxins or environmental pollutants, but they are also widely used as drugs for various purpose including anticancer agent. A novel biphenolic compound, bis(2-hydroxy-3-tert-butyl-5-methylphenyl)methane (GERI-BPO02-A) was isolated from the fermentation broth of Aspergillus fumigatus F93 previously, and it has revealed cytotoxicity against human solid tumor cells. Its effective doses that cause 50% inhibition of cell growth in vitro against non-small cell lung cancer cell A549, ovarian cancer cell SK-OV-3, skin cancer cell SK-MEL-2 and central nerve system cancer cell XF498 were 8.24, 10.60, 8.83, $9.85\mug/ml$ respectively. GERI-BPO02-A has also revealed cytotoxicity against P-glycoproteinexpressed human colon cancer cell HCT15 and its multidrug-resistant subline HCT15/CL02, and its cytotoxicity was not affected by P-glycoprotein. We have also tested cytotoxicities of structurally related compounds of GERI-BPO02-A such as diphenylmethane, 1,1-bis(3,4dimethylphenyl)ethane, 2,2-diphenylpropane, 2-benzylpyridine, 3-benzylpyridine, $4,4^I-di-tert-butylphenyl$, bibenzyl, $2,2^I-dimethylbibenzyl$, cis-stilbene, trans-stilbene, 3-tert-butyl-4-hydroxy-5-methylphenyisulfide, sulfadiazine and sulfisomidine for studying of structure and activity relationship, and from these data we could suppose that hydroxyl group of GERI-BPO02A conducted important role in its cytotoxicity.

• Asian Pacific Journal of Cancer Prevention
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• 제14권5호
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• pp.3191-3196
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• 2013

Leaf extracts of Cassia alata L (akapulko), traditionally used for treatment of a variety of diseases, were evaluated for their potential antitumor properties in vitro. MTT assays were used to examine the cytotoxic effects of crude extracts on five human cancer cell lines, namely MCF-7, derived from a breast carcinoma, SK-BR-3, another breast carcinoma, T24 a bladder carcinoma, Col 2, a colorectal carcinoma, and A549, a nonsmall cell lung adenocarcinoma. Hexane extracts showed remarkable cytotoxicity against MCF-7, T24, and Col 2 in a dose-dependent manner. This observation was confirmed by morphological investigation using light microscopy. Further bioassay-directed fractionation of the cytotoxic extract led to the isolation of a TLC-pure isolate labeled as f6l. Isolate f6l was further evaluated using MTT assay and morphological and biochemical investigations, which likewise showed selectivity to MCF-7, T24, and Col 2 cells with $IC_{50}$ values of 16, 17, and 17 ${\mu}g/ml$, respectively. Isolate f6l, however, showed no cytotoxicity towards the non-cancer Chinese hamster ovarian cell line (CHO-AA8). Cytochemical investigation using DAPI staining and biochemical investigation using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-a method used to detect DNA fragmentation-together with caspase assay, demonstrated apoptotic cell death. Spectral characterization of isolate f6l revealed that it contained polyunsaturated fatty acid esters. Considering the cytotoxicity profile and its mode of action, f6l might represent a new promising compound with potential for development as an anticancer drug with low or no toxicity to non-cancer cells used in this study.

• Biomolecules & Therapeutics
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• 제25권2호
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• pp.194-201
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• 2017

Lysophosphatidylethanolamine (LPE), a lyso-type metabolite of phosphatidylethanolamine, has been reported to be an intercellular signaling molecule. LPE mobilizes intracellular $Ca^{2+}$ through G-protein-coupled receptor (GPCR) in some cells types. However, GPCRs for lysophosphatidic acid (LPA) were not implicated in the LPE-mediated activities in LPA GPCR overexpression systems or in SK-OV3 ovarian cancer cells. In the present study, in human SH-SY5Y neuroblastoma cells, experiments with $LPA_1$ antagonists showed LPE induced intracellular $Ca^{2+}$ increases in an $LPA_1$ GPCR-dependent manner. Furthermore, LPE increased intracellular $Ca^{2+}$ through pertussis-sensitive G proteins, edelfosine-sensitive-phospholipase C, 2-APB-sensitive $IP_3$ receptors, $Ca^{2+}$ release from intracellular $Ca^{2+}$ stores, and subsequent $Ca^{2+}$ influx across plasma membranes, and LPA acted on $LPA_1$ and $LPA_2$ receptors to induce $Ca^{2+}$ response in a 2-APB-sensitive and insensitive manner. These findings suggest novel involvements for LPE and LPA in calcium signaling in human SH-SY5Y neuroblastoma cells.

• 생명과학회지
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• 제15권5호
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• pp.802-808
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• 2005

사람의 Disabled-2 (Dab2)는 정상세포에서 c-Fos의 발현을 억제하여 세포 성장을 조절하는 암억제 유전자로 추정되어 지고 있다. 많은 암세포에서 Dab2는 유방과 난소의 정상세포에서는 발현이 되지만, 약 $85\%$의 유방과 난소의 종양세포에서는 발현이 줄어들거나, 발현이 억제되는 것으로 알려져 있다. 본 연구에서는 bisulfite 반응에 의한 염기서열 분석법과 MSP방법 등을 이용하여 유방암 세포주인 MDA MB-231세포에서 Dab2 유전자의 promoter상에 존재하는 Cpg island의 methylation된 상태를 분석하였다. 그 결과, 사람의 정상 자궁내막세포에서는 Dab2 promoter 부위가 완전하게 methylation되어 있지 않았다. 그러나 MDA MB-231세포에서는 TATA box 근처 의 CpG dinucleotide에서 비정상적으로 methylation되어 있었다. 이런 비정상적인 CpG dinucleotide의 methylation은 MDA MB-231세포를 5-azacytidine으로 처리하였을 때 methylation이 풀리고, Dab2의 발현이 회복되는 것으로 나타났다. 따라서 인간 유방암 세포주인 MBA MB-231세포에서 Dab2의 발현억제는 Dab2 유전자의 promoter부위의 CpG island의 비정상적인 methylation과 관련이 있는 것으로 여겨진다.

• 동국한의학연구소논문집
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• 제9권
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• pp.139-154
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• 2000

한약재(韓藥材)의 암치료(癌治療)에 응용(應用) 가능성(可能性)을 연구(硏究)한 23종(種)의 논문(論文)을 대상(對象)으로 하여 문헌적(文獻的)으로 고찰(考察)한 바, 한의학(韓醫學)에서는 청열해독(淸熱解毒), 소종지혈(消腫止血), 활혈화어(活血化瘀), 이기보비양혈(理氣補脾養血), 화담연견(化痰軟堅), 건비화습(健脾化濕), 이기산결(理氣散結)하는 한약재(韓藥材)를 이용하여 부정법(扶正法), 거사법(祛邪法), 부정거사법(扶正祛邪法)으로써 암치료(癌治療)에 응용(應用)하고 있으며, 실험(實驗)에 사용(使用)된 약물(藥物)은 총(總) 103종(種)으로 이 중(中)에서 어성초(魚腥草), 저령, 천산갑(穿山甲), 오수유(吳茱萸), 목향(木香), 흑축(黑丑) 등의 항암효과(抗癌效果)가 우수(憂愁)한 것으로 나타났는데, 특히 어성초(魚腥草)는 암세포주(癌細胞柱)에 대한 감수성(感受性)도 높게 나타났지만 정상세포(正常細胞)에 대한 억제효과(抑制效果)는 낮게 나타났고, 오수유(吳茱萸), 목향(木香), 흑축(黑丑)은 20여종의 암세포주(癌細胞柱)에 모두 높은 세포독성(細胞毒性)이 나타났으며, 삼백초(三白草)는 HT-29, melanoma, SK-MEL-5에, 지모(知母)는 난소암(卵巢癌) 세포주(細胞柱)에, 형개(荊芥)는 HT-29 세포주(細胞柱)에 특히 높은 활성(活性)을 보였다. 또한 실험(實驗)에 사용된 암세포주(癌細胞柱) 중에서 생쥐 유래의 P815, Yac-1 세포주(細胞柱)와 사람의 Sarcoma 180, K562, SNU-1 세포주(細胞柱)가 가장 다용(多用)되었다.

• 한국임상수의학회지
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• 제32권6호
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• pp.530-535
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• 2015

11년령의 암컷 미니어처 푸들이 4개월의 혈흉으로 본 병원에 의뢰되었다. 신체검사에서, 비록 청진상에서 오른쪽 흉곽의 심음이 희미했으나 환축은 기민한 상태였다. 방사선 상에서 흉강은 흉수로 가득 차 있었다. 초음파 상에서는 양쪽 난소는 낭포성 변화가 관찰되었고 간에서 여러 개를 결절을 확인했다. 컴퓨터 단층 촬영에서 오른쪽 중간엽으로 들어가는 기관지의 허탈을 확인한 후에 거칠게 보였던 오른쪽 폐의 음영은 오른 중간엽 폐염전으로 진단되었다. 진단 5일후에 오른쪽 5번째 갈비뼈 사이로 접근하여 중간엽을 절제하였고 동시에 난소자궁적출술도 실시되었다. 병리조직학적 검사에서 양쪽 난소에서는 유두상 선암종이 나타났고, 중간엽에서는 난소에서 전이된 것으로 의심되는 선암종이 진단되었다. 환축은 2달동안 순조롭게 회복되었다. 그러나 4달 후에 환축은 호흡곤란으로 내원하였다. 방사선 상에서 흉수와 오른쪽 앞엽과 왼쪽 뒤엽이 허탈 되어 있었다. 그리고 흉수에서 전이로 의심되는 악성 상피종 세포가 관찰되었다. 보호자에게 항암 치료를 권해드렸으나 보류하셨고 환축은 퇴원하였다. 본 보고의 목적은 종양으로 인한 출혈성 흉수로 폐염전이 발생할 수 있는 드문 증례를 보고 하기 위함이다.

• Journal of Nutrition and Health
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• 제41권1호
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• pp.13-21
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• 2008

본 실험은 인돌의 인체 대장암세포의 경과 및 전이억제와 TJ 활성 조절에 미치는 영향을 알아보기 위해 실험하였다. 인돌은 십자화 야채류인 양배추, 컬리플라워, 브로클리 등에 존재하는 glucosinolate, glucobrassicin의 대사산물 이다. 본 연구의 결과는 인돌이 대장암 세포 HT-29에서 농도 의존적으로 세포증식 저해를 나타내었다. 상처회복 실험을 통한 세포이동성과 세포 침윤성 실험결과 인돌이 암세포의 이동과 침윤성을 억제하였고 투과성상피세포의 전기적 저항성 측정치는 인돌 처리 세포에서 증가하였다. HT-29 세포에서 과발현을 나타내는 밀착결합 단백질인 claudin-1, claudin-5 발현은 인돌 처리로 유전자의 전사수준과 단백질 수준에서 유의적인 감소를 나타내었다. 이상의 결과에서 인돌이 HT-29 세포의 밀착결합과 그 구성 단백질 중 claudin 발현 현상을 회복시키므로 암 경과와 전이 억제를 나타내었다. 결론적으로, 천연 항암화합물인 인돌은 대장암 세포 HT-29에서 밀착결합 단백질인 claudin-1, -5을 억제하여 밀착결합을 활성화하므로 암 진행과 전이를 억제할 수 있는 인돌에 의한 새로운 기전을 보고합니다.