• 한국자기공명학회논문지
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• 제21권1호
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• pp.31-43
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• 2017

Together with radiotherapy, chemotherapy using cytotoxic agents is one of the most common therapies in cancer. Metabolic changes in cancer cells are drawing much attention recently, but the metabolic alterations by anticancer agents have not been much studied. Here, we investigated the effects of commonly used cytotoxic agents on lung normal cell MRC5 and lung cancer cell A549. We employed cis-plastin, doxorubicin, and 5-Fluorouracil and compared their effects on the viability and metabolism of the normal and cancer cell lines. We first established the concentration of the cytotoxic reagents that give differences in the viabilities of normal and cancer cell lines. In those conditions, the viability of A549 decreased significantly, whereas that of MRC5 remained unchanged. To study the metabolic alterations implicated in the viability differences, we obtained the metabolic profiles using $^1H$-NMR spectrometry. The $^1H$-NMR data showed that the metabolic changes of A549 cells are more remarkable than that of MRC5 cells and the effect of 5-FU on the A549 cells is the most distinct compared to other treatments. Heat map analysis showed that metabolic alterations under treatment of cytotoxic agents are totally different between normal and cancer cells. Multivariate analysis and weighted correlation network analysis (WGCNA) revealed a distinctive metabolite signature and hub metabolites. Two different analysis tools revealed that the changes of cell metabolism in response to cytotoxic agents were highly correlated with the Warburg effect and Reductive lipogenesis, two pathways having important effects on the cell survival. Taken together, our study addressed the correlation between the viability and metabolic profiles of MRC5 and A549 cells upon the treatment of cytotoxic anticancer agents.

• 대한한의학방제학회지
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• 제23권1호
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• pp.101-110
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• 2015

Objectives : The purpose of this study was to investigate the anti-cancer effects of Oldenlandia diffusa extract on WiDr human colorectal adenocarcinoma cells. Methods : We examined cell death by (3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide) MTT assay and the caspase 3 and 9 activity assay with Oldenlandia diffusa extract. To examine the inhibitory effects of Oldenlandia diffusa extract, we performed a cell cycle (sub-G1) analysis and mitochondrial membrane potential for the WiDr cells after 24 hours with Oldenlandia diffusa extract. Results : 1. Oldenlandia diffusa extract induced cell death in WiDr cells. 2. The sub-G1 peak was increased by Oldenlandia diffusa extract in WiDr cells. 3. Oldenlandia diffusa extract leads to increase the mitochondrial membrane depolarization in WiDr cells. 4. Oldenlandia diffusa extract increases caspase 3 and 9 activities in WiDr cells. 5. Oldenlandia diffusa extract combined with several anti-cancer drugs (paclitaxel, 5-fluorouracil, cisplatin, ectoposide, doxorubicin and docetaxel) markedly inhibited the growth of WiDr cells compared to Oldenlandia diffusa extract and anti-cancer drugs alone. Conclusions : Oldenlandia diffusa extract has an apoptotic role in human colorectal cancer cells and a potential role in developing therapeutic agents against colorectal cancer.

• 대한한의학회지
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• 제27권4호
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• pp.62-73
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• 2006

Objective : This study aimed to investigate the effect of SHD on myelosuppression using an animal model for therapeutic evidence supporting clinical positive results. Methods : After determining the optimal concentration of 5-FU as 300 mg/kg for developing the mouse model, ICR mice or BALB/c mice were administered with SHD, and several blood parameters, including hematopoietic cytokines, colony forming activity and histological findings, were examined to evaluate the effects. Results : SHD restored the WBC and hemoglobin, and showed effects on maintaining body weight, producing GM-CSF and IL-3 and stem cell colony forming activity in accordance with histological relative entirety on bone marrow. Conclusion : SHD is an herbal drug having therapeutic effects on myelosuppression. Thus, it could be prescribed to cancer patients undergoing chemo-therapies or radio-therapies in the process of cancer treatment.

• 대한한의학회지
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• 제27권4호
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• pp.48-56
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• 2006

Objectives : This study is aimed to elucidate anti-hepatoma activity of Coptis Chinensis Extract (CCE) and evaluate its effect on proliferation of human hepatoma Hep G2 cells. Methods : To identify CCE and control the quality, we performed fingerprinting by high-performance thin layer chromatography (HPTLC). To investigate effects of CCE on anti-hepatoma activity, we measured cytotoxicity against Hep G2 cells compared with treatment of paclitaxel and 5-fluorouracil (5-FU). To examine the mechanism of inhibitory effect of CCE on Hep G2 cell proliferation, cell cycle distribution was evaluated using fluorescent activated cell sorter (FACS) Result : CCE showed a significant effect that arrests Hep G2 cells at the G2/M phase of the cell cycle. CCE combined with paclitaxel inhibited synergistically cell growth of Hep G2 cells. Conclusion : CCE may present anticancer effects through inhibition of hepatocellular carcinoma (HCC) cell proliferation via G2/M arrest, and may be a useful anticancer agent for HCC.

• Journal of Microbiology and Biotechnology
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• 제14권6호
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• pp.1182-1189
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• 2004

Cytosine deaminase (cytosine aminohydrolase, EC 3.5.4.1) stoichiometrically catalyzes the hydrolytic deamination of cytosine and 5-fluorocytosine to uracil and 5-fluorouracil, respectively. The intracellular cytosine deaminase from Chromobacterium violaceum YK 391 was purified to apparent homogeneity with 272.9-fold purification with an overall yield of $13.8\%$. The enzyme consisted of dimeric polypeptides of 63 kDa, and the total molecular mass was calculated to be approximately 126 kDa. Besides cytosine, the enzyme deaminated 5-fluorocytosine, cytidine, 6-azacytosine, and 5-methylcytosine, but not 5-azacytosine. Optimum pH and temperature for the enzyme reaction were 7.5 and $30^{\circ}C$, respectively. The enzyme was stable at pH 6.0 to 8.0, and at 30T for a week. About $70\%$ of the enzyme activity was retained at $60^{\circ}C$ for 5 min. The apparent $K_{m}$ values for cytosine, 5-fluorocytosine, and 5-methylcytosine were calculated to be 0.38 mM, 0.87 mM, and 2.32 mM, respectively. The enzyme activity was strongly inhibited by 1 mM $Hg^{2+},\;Zn^{2+},\;Cu^{2+},\;Pb^{2+},\;and\;Fe^{3+}$, and by o-phenanthroline, $\alpha,\;{\alpha}'$-dipyridyl, p-choromercuribenzoate, N-bromosuccinimide, and cWoramine­T. In addition, the enzyme activity was strongly inhibited by I mM 2-thiouracil, and weakly inhibited by 2-thiocytosine, or 5-azacytosine. Finally, intracellular and extracellular cytosine deaminases from Chromobacterium violaceum YK 391 were found to have a different optimum temperature, apparent $K_{m}$ value, and molecular mass.

• 대한두경부종양학회지
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• 제6권1호
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• pp.11-23
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• 1990

Systemic chemotherapy is usually regarded as the standard treatment for palliation in patients with recurrent or metastatic cancer who have failed the definite local treatment with surgery and/or radiotherapy. Recently, with the introduction of more active chemotherapeutic agents and combinations, systemic chemotherapy is being increasingly used before or after local therapy in patients with previously untreated locally advanced head and neck cancer. The most active agents for the head and neck caner are methotrexate, 5-fluorouracil (5-FU), cisplatin and bleomycin. The overall response rates to each of these four drugs are 15-30% expecially when used as first line therapy. But most of these responses are partial with a mean duration of 3-5 months. Various combinations with methotrexate, 5-FU, cisplatin, and bleomycin have been tried with overall response rates of 50-90%, and 10-20% of complete responses. The introduction of chemotherapy prior to local therapy, induction chemotherapy, has been investigated with improved survivals in patients with complete response, especially pathologic, though improvement in overall survival has not been proved yet after the induction chemotherapy. Other therapeutic modalities, such as 'Sandwich' chemotherapy between surgery and radiotherapy, concomittent chemo-radiotherapy and post local treatment adjuvant chemotherapy have been pursued with some hopeful results but these trials should be compared with prospective randomized Phase III trials. To increase the response rates and enhance the survival, important work still remains; 1. Identification of better prognostic factors, 2. Improvement in staging, 3. Development of more active and safter chemotherapeutic agents, 4. Identification of the proper sequence for the addition of chemotherapy to multimodality treatment, and 5. Testing the value of such chemotherapy in locally advanced cancer patients.

• 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.

• 대한약침학회지
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• 제15권3호
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• pp.19-30
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• 2012

Objectives: Many efforts have shown multi-oncologic roles of galectin-3 for cell proliferation, angiogenesis, and apoptosis. However, the mechanisms by which galectin-3 is involved in cell proliferation are not yet fully understood, especially in human colon cancer cells. Methods: To cluster genes showing positively or negatively correlated expression with galectin-3, we employed human colon cancer cell lines, SNU-61, SNU-81, SNU-769B, SNU-C4 and SNU-C5 in high-throughput gene expression profiling. Gene and protein expression levels were determined by using real-time quantitative polymerase chain reaction (PCR) and western blot analysis, respectively. The proliferation rate of human colon cancer cells was measured by using a 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Results: Expression of ${\gamma}$-aminobutyric acid B receptor 1 (GABABR1) showed a positive correlation with galectin-3 at both the transcriptional and the translational levels. Down-regulation of galectin-3 decreased not only GABABR1 expression but also the proliferation rate of human colon cancer cells. However, Korean herbal extract, HangAmDan-B (HAD-B), decreased expression of GABABR1 without any expressional change of galectin-3, and offset ${\gamma}$-aminobutyric acid (GABA)-enhanced human colon cancer cell proliferation. Conclusions: Our present study confirmed that GABABR1 expression was regulated by galectin-3. HAD-B induced galectin-3-independent down-regulation of GABABR1, which resulted in a decreased proliferation of human colon cancer cells. The therapeutic effect of HAD-B for the treatment of human colon cancer needs to be further validated.

• 한국미생물·생명공학회지
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• 제30권4호
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• pp.367-372
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• 2002

본 연구에서는 cytosine deaminase(CODase)의 활성이 비교적 높은 Chromobacterium violaceum YK 391의 생육과 세포내 CODase의 최적 배양조건을 규명한 결과, soluble starch 0.75%, peptone 1.5%, yeast extract 0.1%, meat extract 0.1%, NaCl 0.01%, $K_2HPO_4$ 0.05%였다. 배지의 초기 pH 6.5에서 7.5까지 생육과 더불어 효소생성이 가장 양호했지만 산성 혹은 염기성 쪽으로 갈수록 균의 증식의 둔화와 더불어 효소생성 정도도 낮아졌다. 효소 생성에 미치는 배양 온도의 영향을 검토한 결과, 균의 생육은 저온보다는 $28^{\circ}C$에서 $30^{\circ}C$의 온도에서 양호하였으며, 40도씨 이상의 고온에서는 생육 및 효소 생성이 점차적으로 낮아졌고 균의 증식과 배양일수에 따른 효소활성에 있어서 균은 12시간의 유도기를 거쳐 배양 72시간 이후에 최대 생육도를 나타냈으며 균의 증식과 효소 생성 정도는 거의 일치하는 양상을 나타냈다.

• Asian Pacific Journal of Cancer Prevention
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• 제14권1호
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• pp.381-386
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• 2013

Aims: The aim of this study was to investigate the effects of adjuvant chemotherapy cycles on the prognosis of patients with post-operative stomach cancer through retrospective analysis. Methods: A total of 128 patients with gastric cancer who underwent gastrectomy, followed by adjuvant chemotherapy consisting of epirubicin, cisplatin or oxaliplatin, leucovorin, and 5-fluorouracil, according to a defined schedule, were divided into three groups according to the number of chemotherapy cycles: Group I (<6 cycles); Group II (6 cycles); and Group III (>6 cycles). Results: The 5-year overall survival (OS) was 20.8% in Group I, 45.0% in Group II, and 42.9% in Group III, with a median follow-up of 43 months. The 5-year relapse-free survival (RFS) was 15.1% in Group I, 40% in Group II, and 40% in Group III. The OS and RFS in Groups II and III were significantly better than in Group I (OS, p = 0.002 and p=0.003; RFS, P<0.001 and P=0.002). There was no difference in OS (p = 0.970) or in RFS (p = 0.722) between Groups II and III. Multivariate Cox hazard analysis determined that the number of adjuvant chemotherapy cycles was an independent factor that influenced OS and RFS. Conclusion: Six cycles of adjuvant chemotherapy gave encouraging outcomes in patients with resectable gastric cancer. Further prospective randomized controlled investigations are warranted in a multi-center setting.