• 제목/요약/키워드: Antineoplastic activity

검색결과 62건 처리시간 0.028초

L5187Y 세포에 대한 불화피리미딘 대사억제제 독성에 관한 Benzylacyclouridine의 영향 (The Effects of 5-benzylacyclouridine on the Cytotoxicities of Fluorinated Pyrimidine Antimetabolic Agents in L5178Y Cells)

  • 이강현;차승만
    • 대한약리학회지
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    • 제26권1호
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    • pp.91-100
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    • 1990
  • Benzylacyclouridines (BAU and BBAU)는 uridine phosphorylase (UrdPase)의 선택적이고 강력한 상경억제제이다. 보고된 바에 의하면 (Cancer Res., 44: 1852, 1984) Benzylacyclouridines가 5-fluoro-2'-deoxyuridine (FdUrd)의 인체 암세포에 대한 독성을 증가시켜 준다고 하였지만, L5187Y 세포를 사용한 본 실험에서는 Benzylacyclouridines가 FdUrd를 포함하여 5-fluorouridine (FUra) 모두에 대해 조금도 세포 독성을 증가시키지 못하였을 뿐만아니라, 오히려 세포를 그들 독성으로부터 투여량에 비례하여 보호하였다. 복강내 주사에 의한 생체실험에서도 Benzylacyclouridines는 5-fluorinated pyrimidine에 의한 L5187Y를 지닌 쥐(mouse)의 life-span을 연장시켜 주지 못하였다. 본 실험에서 Benzylacyclouridines가 기대했던 fluorinated pyrimidine 항암제의 효과를 증진시키지 못한 이유는 nucleosides의 anabolism이 UrdPase와 orotate phosphoribosyltransferase이 의한 sequential 작용에 의하던가 또는 Benzylacyclouridines에 의한 nucleosides의 수송억제에 의하던가, 아니면 두가지 다 복합적으로 작용한 결과로 생각된다.

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Anticancer Effects of Curcuma C20-Dialdehyde against Colon and Cervical Cancer Cell Lines

  • Chaithongyot, Supattra;Asgar, Ali;Senawong, Gulsiri;Yowapuy, Anongnat;Lattmann, Eric;Sattayasai, Nison;Senawong, Thanaset
    • 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.

Oxaliplatin, 5-Fluorouracil and Leucovorin (FOLFOX-4) as First Line Chemotherapy in Elderly Patients with Advanced Gastric Cancer

  • Haghighi, Shirin;Kasbkar, Hadi;Esmaeilpour, Keihan;Yasaei, Mehrdad
    • Asian Pacific Journal of Cancer Prevention
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    • 제17권7호
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    • pp.3277-3280
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    • 2016
  • Background: Gastric cancer is considered the fourth most common cancer and second most common cause of cancer-related mortalities worldwide. Gastric cancer develops more frequently among elderly. The oxaliplatin/5FU/leucovorin (FOLFOX) regimen has shown a notable activity against gastric cancer. Aim: To evaluate the responses and complications of FOLFOX-4 regimen as first line chemotherapy in elderly patients with advanced gastric cancer. Materials and Methods: From October 2014 to November 2015, a total of 21 patients with metastatic or local AGC (advanced gastric cancer) were analyzed. All patients were administered a FOLFOX-4 regimen consisting of a 2h infusion of oxaliplatin $85mg/m^2$ (day 1), continuous infusion of $1000mg/m^2$ 5-Fu in 24h., and leucovorin $200mg/m^2$ in 2h infusion as a first-line chemotherapy. Results: A total of 18 patients were assessable for efficacy and toxicity. One of 18 patients achieved a complete response, and 12 had partial responses, giving an overall response rate of 72.6%. Three (16%) patients demonstrated stable disease and 2 (12%) progression. The median progression free survival was 7.3 months, and the median overall survival was 11.9 months. One patient had grade 3 neuropathy. No other grade 3 or 4 NCI-CTC were seen. Conclusions: The FOLFOX-4 regimen used in our study was both active and acceptable for AGC in elderly patients as neoadjuvant and main therapy.

Insertion Mutation in HMG-CoA Lyase Increases the Production Yield of MPA through Agrobacterium tumefaciens-Mediated Transformation

  • Dong, Yuguo;Zhang, Jian;Xu, Rui;Lv, Xinxin;Wang, Lihua;Sun, Aiyou;Wei, Dongzhi
    • Journal of Microbiology and Biotechnology
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    • 제26권11호
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    • pp.1924-1932
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    • 2016
  • Mycophenolic acid (MPA) is an antibiotic produced by Penicillium brevicompactum. MPA has antifungal, antineoplastic, and immunosuppressive functions, among others. ${\beta}-Hydroxy-{\beta}-methylglutaryl-CoA$ (HMG-CoA) lyase is a key enzyme in the bypass metabolic pathway. The inhibitory activity of HMG-CoA lyase increases the MPA biosynthetic flux by reducing the generation of by-products. In this study, we cloned the P. brevicompactum HMG-CoA lyase gene using the thermal asymmetric interlaced polymerase chain reaction and gene walking technology. Agrobacterium tumefaciens-mediated transformation (ATMT) was used to insert a mutated HMG-CoA lyase gene into P. brevicompactum. Successful insertion of the HMG-CoA lyase gene was confirmed by hygromycin screening, PCR, Southern blot analysis, and enzyme content assay. The maximum MPA production by transformants was 2.94 g/l. This was 71% higher than wild-type ATCC 16024. Our results demonstrate that ATMT may be an alternative practical genetic tool for directional transformation of P. brevicompactum.

Anti-Angiogenic Activity of Gecko Aqueous Extracts and its Macromolecular Components in CAM and HUVE-12 Cells

  • Tang, Zhen;Huang, Shu-Qiong;Liu, Jian-Ting;Jiang, Gui-Xiang;Wang, Chun-Mei
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권5호
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    • pp.2081-2086
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    • 2015
  • Gecko is a kind of traditional Chinese medicine with remarkable antineoplastic activity. However, undefined mechanisms and ambiguity regarding active ingredients limit new drug development from gecko. This study was conducted to assess anti-angiogenic properties of the aqueous extracts of fresh gecko (AG) or macromolecular components separated from AG (M-AG). An enzyme-linked immunosorbent assay (ELISA) approach was applied to detect the vascular endothelial growth factor (VEGF) secretion of the tumor cells treated with AG or M-AG. The effect of AG or M-AG on vascular endothelial cell proliferation and migratory ability was analyzed by tetrazolium dye colorimetric method, transwell and wound-healing assays. Chick embryo chorioallantoic membrane (CAM) assays were used to ensure the anti-angiogenic activity of M-AG in vivo. The results showed that AG or M-AG inhibited the VEGF secretion of tumor cells, the relative inhibition rates of AG and M-AG being 27.2% and 53.2% respectively at a concentration of $20{\mu}L/mL$. AG and M-AG inhibited the vascular endothelial (VE) cell proliferation with IC50 values of $11.5{\pm}0.5{\mu}L/mL$ and $12.9{\pm}0.4{\mu}L/mL$ respectively. The VE cell migration potential was inhibited significantly (p<0.01) by the AG (${\geq}24{\mu}L/mL$) or M-AG (${\geq}12\mu}L/mL$) treatment. In vivo, neovascularization of CAM treated with M-AG was inhibited significantly (p<0.05) at a concentration of ${\geq}0.4{\mu}L/mL$. This study provided evidence that anti-angiogenesis is one of the anti-tumor mechanisms of AG and M-AG, with the latter as a promising active component.

Cisplatin으로 유도된 신손상 마우스 모델에 대한 발효홍삼의 예방효능 (Preventive effect of fermented red ginseng on cisplatin-induced nephrotoxicity mouse)

  • 현자경;권오준;이주영;노성수;서영배
    • Journal of Applied Biological Chemistry
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    • 제59권2호
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    • pp.113-124
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    • 2016
  • 홍삼은 인삼을 찌고 말리는 과정을 거쳐 제조한 것으로 많은 약리 및 생리활성이 알려져 있다. Cisplatin은 항암제로 사용되고 있으나 부작용으로 골수억제, 위장관계독성, 신경독성, 신독성 등이 보고되어있다. 특히 cisplatin이 신장에 집중적으로 축적됨으로써 투여환자의 25-30%에서 신장독성이 유발된다. 따라서 본 실험에서는 발효홍삼을 이용한 cisplatin의 부작용인 신독성예방효능을 확인하고자 하였다. 시료에 따른 DPPH와 ABTS 라디칼소거능을 실험 결과 RG8F3에서 가장 우수한 소거능을 확인하였고 따라서 RG0SF0와 RG8F3 간의 비교실험이 가능할 것으로 사료되었다. 동물실험은 정상군, 대조군, RG0SF0 투여군 및RG8F3 투여군 4그룹으로 나누었다. 약물투여군은 200 mg/kg/day의 농도로 4일간 투여한 후,cisplatin은 20 mg/kg으로 대조군 및 약물투여군에복강주사하였다. RG8F3 투여한 결과 대조군과 비교하여 GSH의 수치는 증가하였고 ROS, BUN, creatinine 및 염증인자들의 감소를 보였다. 조직학적 결과에서도 신손상으로 인한 변형이 거의 없었다. 결론적으로 발효홍삼은 cisplatin으로 유발되는 신 손상 예방에 유의한 효과를 보이는 것으로 사료된다.

대장암 항암 화학요법의 처방 오류 평가 및 개선안 제시 (Guideline of Improvement and Evaluation of Prescribing Errors in Colorectal Chemotherapy)

  • 임현수;임성실
    • 한국임상약학회지
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    • 제23권2호
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    • pp.158-166
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    • 2013
  • Background: Colorectal cancer shows a significant increase in South Korea due to westernization of diet, lack of dietary fiber, drinking and smoking, irregular defecation. There are surgery, chemotherapy, radiation therapy in treatment of colorectal cancer. There may be a medication errors in the process of chemotherapy because of its high toxicity, narrow therapeutic index and the health status of cancer patients. Consequently medication errors can cause increasing the risk of death, prolonging hospital stay and increasing the cost. Among medication errors on medication use process, prescribing errors are of particular concern due to higher risk of serious consequences. It is important for pharmacist to prevent the prescribing errors before reaching patient. Therefore we analyzed the prescriptions of colorectal cancer, classified prescribing errors, suggested guideline to reduce prescribing errors and verified the importance of pharmacist's role in prevention of medication errors activity. Methods: We collected the numbers of prescriptions of colorectal cancer(n=2,373) through anti cancer management program and EMR and analyzed the errors of prescriptions by categories from Oct 1st 2011 to Sep 30th 2012 at Chungbuk National University Hospital. We reviewed the prescriptions as follows - patients' characteristics, the result of test, previous prescriptions, characteristics of antineoplastic agents and patients' allergy, drug sensitivity, adverse events. Prescriptions are classified into inpatient and outpatient and analyzed the errors of prescriptions by categories (dosage form, dose, input, diluents, regimen, product). Results: Total prescription number of inpatient and outpatient of colorectal cancer was 1,193 and 1,180 and that of errors was 107(9%) and 22(1.9%), respectively. In case of errors of categories, the number of errors of dosage form is 69 and 8, errors of dose is 15 and 5, errors of input is 9 and 9 in inpatient and outpatient prescriptions, respectively. Errors of diluents is 8, errors of regimen is 3, errors of product is 3 in only inpatient prescriptions. In case of errors of categories by inpatient department, the number of errors of dosage form is 34 and 35, errors of dose is 7 and 8, errors of input is 6 and 3, errors of diluents is 4 and 4, errors of regimen is 2 and 1, errors of product is 2 and 1 in SG and HO, respectively. In case of outpatient department, the number of errors of dosage form is 8 in HO, errors of dose is 5 in HO, errors of input is 5 and 4 in SG and HO, respectively. Conclusions: The rate of errors of inpatient is higher than that of outpatient. Junior doctors are engaged in prescriptions of inpatient and pharmacist need to pay attention to review all prescriptions. If prescribing errors are discovered, pharmacist should contact the prescriber and correct the errors without delay. The guideline to reduce prescribing errors might be upgrading software of anti cancer management program, education for physicians as well as pharmacists and calling prescriber's attention to preventing recurrence of errors.

Anti-Cancer Effect of the Combination of Thiacremonone and Docetaxel by Inactivation of NF-κB in Human Cancer Cells

  • Ban, Jung-Ok;Cho, Jin-Suk;Hwang, In-Guk;Noh, Jin-Woo;Kim, Wun-Jae;Lee, Ung-Soo;Moon, Dong-Cheul;Jeong, Heon-Sang;Lee, Hee-Soon;Hwang, Bang-Yeon;Jung, Jae-Kyung;Han, Sang-Bae;Hong, Jin-Tae
    • Biomolecules & Therapeutics
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    • 제17권4호
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    • pp.403-411
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    • 2009
  • Thiacremonone, the main component isolated from heated garlic (Allium sativum L.), is interested for using as a cancer preventive or therapeutic agent since garlic has been known to be useful plant in the treatment of cancers. Nuclear factor kappaB (NF-${\kappa}B$) is constitutively activated in the prostate cancer and activation of NF-${\kappa}B$ is implicated in drug resistance in cancer cells. Docetaxel, a semisynthetic analog of paclitaxel, is an antineoplastic drug widely used for advanced various cancer. In previous studies, we found that thiacremonone inhibited activation of NF-${\kappa}B$ in cancer cells and marcrophages. In the present study, we investigated whether thiacremonone could increase susceptibility of prostate cancer cells (PC-3 and DU145) to docetaxel via inactivation of NF-${\kappa}B$. We found that the combination treatment of thiacremonone (50 ${\mu}g$/ml) with docetaxel (5 nM) was more effective in the inhibition of prostate cancer cell growth and induction of apoptosis accompanied with the significant inhibition of NF-${\kappa}B$ activity than those by the treatment of thiacremonone or docetaxel alone. It was also found that NF-${\kappa}B$ target gene expression of Bax, caspase-3 and caspase-9 was much more significantly enhanced, but the expression of Bcl-2 was also much more significantly inhibited by the combination treatment. These results indicate that thiacremonone inhibits NF-${\kappa}B$, and enhances the susceptibility of prostate cancer cells to docetaxel. Thus, thiacremonone could be useful as an adjuvant anti-cancer agent.

Valproic acid와 HS-1200의 병용처리가 사람골육종세포에 미치는 세포자멸사 효과에 대한 연구 (Apoptotic Effect of Co-Treatment with Valproic Acid and HS-1200 on Human Osteosarcoma Cells)

  • 김덕한;이기현;김인령;곽현호;박봉수;정성희;고명연;안용우
    • Journal of Oral Medicine and Pain
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    • 제35권3호
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    • pp.165-175
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    • 2010
  • Valproic acid(VPA)는 아주 잘 알려진 항경련제로서, 30년 동안 간질치료제로서 사용되어져 왔다. VPA는 1997년에 최초로 원시 신경외배엽성 암세포의 증식 억제와 분화를 유도하는 항암제의 효능이 밝혀졌다. 그리고 VPA의 항암효과는 히스톤탈 아세틸화효소억제제의 기전에 기인한다고 규명되었다. 담즙산과 합성담즙산유도체가 여러 종류의 암세포에 세포자멸사(apoptosis)를 유도하며, 항암효과가 있다고 알려져 있다. 또한 합성 chenodeoxycholic acid(CDCA) 유도체가 여러 가지 암세포에 유도한 세포자멸사 연구들이 보고되어져 왔다. 본 연구는 히스톤탈아세틸화효소억제제인 VPA와 합성 CDCA 유도체인 HS-1200의 병용처리가 사람골육종세포에 효과적인 상승 세포자멸사 효과가 있는지를 알기 위해서 수행되었다. VPA과 HS-1200의 병용처리가 단독처리에 비해서 효과적인 세포생존율 감소가 있는지 확인하기 위해서 trypan-blue법을 시행하였고, 세포자멸사의 유도와 증가를 확인하기 위해서 Hoechst 염색법, flow cytometry(DNA hypoploidy와 MMP 측정), Western bot 분석법 그리고, 면역형광염색법을 수행하였다. 병용처리 된 사람골육종세포는 단독처리 된 사람골육종세포에서 거의 관찰할 수 없었던 많은 핵 응축, DNA 조각남, 사립체막 전위와 DNA 양의 감소, cytochrome c의 세포질로의 유리, AIF의 핵으로의 이동, caspase-7, caspase-3 그리고 PARP의 파괴와 같은 세포자멸사 증거를 보였다. 48시간 동안 1 mM의 VPA와 $25\;{\mu}M$ HS-1200을 각기 단독처리 한 결과에서는 세포자멸사를 유도 못했으나, 병용처리한 결과에는 아주 탁월한 세포자멸사의 유도를 보였다. 이러한 병용처리 결과는 사람골육종의 새로운 치료적 전략으로 응용될 수 있다고 생각한다.

Valproic acid와 17AAG의 병용처리가 사람골육종세포에 미치는 세포자멸사 효과에 대한 연구 (Apoptotic Effect of Co-Treatment with Valproic Acid and 17AAG on Human Osteosarcoma Cells)

  • 박준영;박세진;김인령;박봉수;정성희;고명연;안용우
    • Journal of Oral Medicine and Pain
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    • 제36권1호
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    • pp.11-20
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    • 2011
  • Valproic acid(VPA)는 아주 잘 알려진 항경련제로서, 30년 동안 간질치료제로서 사용되어져 왔다. VPA는 1997년에 최초로 항암제의 효능이 밝혀졌으며, VPA의 항암효과는 히스톤탈아세틸화효소 억제제의 기전에 기인한다고 규명되었다. 17AAG(17-Allyamnio-17-demethoxygeldanamycin)는 HSP90의 억제제이며, HSP90은 세포증식과 세포생존에 관여하며, 최근 17AAG가 세포자멸사를 유도한다는 연구들이 보고되어지고 있다. 본 연구는 히스톤탈아세틸화효소억제제인 VPA와 HSP90 억제제인 17AAG의 병용처리가 사람골육종세포에 상승 세포자멸사 효과가 있는지를 알기 위해서 수행되었다. VPA과 17AAG의 병용처리가 단독처리에 비해서 효과적인 세포생존율 감소가 있는지 확인하기 위해서 trypan-blue법을 시행하였고, 세포자멸사의 유도와 증가를 확인하기 위해서 Hoechst 염색법, flow cytometry(DNA hypoploidy와 MMP 측정), Western bot 분석법 그리고 면역형광염색법을 수행하였다. 병용처리 된 사람골육종세포는 단독처리 된 사람골육종세포에서 거의 관찰할 수 없었던 핵 응축과 조각남, 사립체막 전위와 DNA 양의 감소, cytochrome c의 세포질로의 유리, AIF의 핵으로의 이동, caspase-3과 caspase-7의 파괴 및 PARP의 분절화와 같은 세포자멸사 증거를 보였다. 48시간 동안 1 mM의 VPA와 0.5 ${\mu}M$ 17AAG을 각기 단독처리 한 결과에서는 세포자멸사를 유도 못했으나, 병용처리한 결과에는 아주 탁월한 세포자멸사의 유도를 보였다. 이러한 병용처리 결과는 사람골육종의 새로운 치료적 전략으로 응용될 수 있다고 생각한다.