• Asian Pacific Journal of Cancer Prevention
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• v.15 no.17
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• pp.7037-7041
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• 2014

Background: 5-Fluorouracil (5-FU) is the most commonly used drug in colon cancer therapy. However, despite impressive clinical responses initially, development of drug resistance to 5-Fu in human tumor cells is the primary cause of failure of chemotherapy. In this study, we established a 5-Fu-resistant human colon cancer cell line for comparative chemosensitivity studies. Materials and Methods: Real time PCR and Western blotting were used to determine gene expression levels. Cell viability was measured by MTT assay. Glucose uptake was assess using an Amplex Red Glucose/Glucose Oxidase assay kit. Results: We found that 5-Fu resistance was associated with the overexpression of Glut1 in colon cancer cells. 5-Fu treatment at low toxic concentration induced Glut1 expression. At the same time, upregulation of Glut1 was detected in 5-Fu resistant cells when compared with their parental cells. Importantly, inhibition of Glut1 by a specific inhibitor, WZB117, significantly increased the sensitivity of 5-Fu resistant cells to the drug. Conclusions: This study provides novel information for the future development of targeted therapies for the treatment of chemo-resistant colon cancer patients. In particular it demonstrated that Glut1 inhibitors such as WZB117 may be considered an additional treatment options for patients with 5-Fu resistant colon cancers.

• Biomolecules & Therapeutics
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• v.30 no.6
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• pp.479-489
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• 2022

5-Fluorouracil (5-FU) remains to be an important chemotherapeutic drug for treating several cancers when targeted therapy is unavailable. Chemoresistance limits the clinical utility of 5-FU, and new strategies are required to overcome the resistance. Reactive oxygen species (ROS) and antioxidants are balanced differently in both normal and cancer cells. Modulating ROS can be one method of overcoming 5-FU resistance. This review summarizes selected compounds and endogenous cellular targets modulating ROS generation to overcome 5-FU resistance.

• Journal of Pharmaceutical Investigation
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• v.38 no.1
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• pp.45-50
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• 2008

5-Fluorouracil (5-FU) is an antimetabolic of the pyrimidine derivatives that is used in chemotherapy for the treatment of several types of cancer. 5-FU have poor oral absorption and short biological half-time and strong side effects. Microneedle introduced to find a solution of problems. Microneedle device with roll was manufactured for transdermal delivery of various drugs. 5-FU was mixed in non-ionic surfactant such as tween 20 and tween 80. Camscope was used to analysis the permeation magnitude of treated skin by microneedle and trypan blue staining. The 5-FU solution with surfactant measured by ZETA-potential analysis system for stability of solution. The skin permeation rate of 5-FU determined by HPLC. We confirmed that cross treated skin was dyed more deeply than parallel treated skin through trypan blue staining. The results indicate that skin permeation rate of 5-FU was increased with the treatment types and treatment times.

• Biomolecules & Therapeutics
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• v.24 no.6
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• pp.604-609
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• 2016

5-fluorouracil (5-FU) is a chemotherapeutic agent commonly used for treatment of solid tumors, including colorectal cancer. However, chemoresistance against 5-fluorouracil (5-FU) often limits its success for chemotherapy and, therefore, finding out appropriate adjuvant(s) that might overcome chemoresistance against 5-FU bears a significant importance. In the present study, we have found that ${\alpha}$-mangostin can sensitize 5-FU-resistant SNUC5/5-FUR colon cancer cells to apoptosis. Exposure of ${\alpha}$-mangostin induced significant DNA damages and increased the intracellular 8-hydroxyguanosine (8-OH-G) and 4-hydroxynonenal (4-HNE) levels in SNUC5 and SNUC5/5-FUR cells. Western blot analysis illustrated that ${\alpha}$-mangostin-induced apoptosis was mediated by the activation of the extrinsic and intrinsic pathways in SNUC5/5-FUR cells. In particular, we observed that Fas receptor (FasR) level was lower in SNUC5/5-FUR cells, compared with SNUC5 cells and that silencing FasR attenuated ${\alpha}$-mangostin-mediated apoptosis in SNUC5/5-FUR cells. Together, our study illustrates that ${\alpha}$-mangostin might be an efficient apoptosis sensitizer that can overcome chemoresistance against 5-FU by activating apoptosis pathway.

• Journal of the Korean Chemical Society
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• v.57 no.1
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• pp.88-93
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• 2013

In order to construct a controlled release system of drugs and to reduce toxic side effects of 5-fluorouracil, the novel ramose chitosan-based-5-fluorouracil microspheres (CS-FU-MS) were prepared. Firstly, using chitosan (CS) as carriers and 5-fluorouracil (5-FU) as a model drug, ramose chitosan-based-5-fluorouracil (CS-FU) was efciently synthesized by chemical crosslinking method through microwave irradiation, drug loading was 10.6%; Secondly, CS-FU-MS were prepared by CS-FU self-assembled under the dialysis conditions and the free 5-FU was encapsulated further at the same time. The size dispersivity of particles is uniform, and the average diameter of the CS-FU-MS was $4{\mu}m$. The drug encapsulation efficiency was 76.1%, and the drug loading was increased to 26.22%. CS-FU-MS maintain the zero-order release time in PBS (pH = 7.4) and HCl/KCl (pH = 1.2) dialysis medium was 40h and 34h respectively, and the cumulative release were 58.89% and 79.33% in 182 h. The results showed that CS-FU-MS have excellent sustained release properties.

• Mycobiology
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• v.51 no.3
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• pp.157-163
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• 2023

Cordyceps fumosorosea is an important species in the genus of Cordyceps, containing a variety of bioactive compounds, including fumosorinone (FU). This study was a ground-breaking assessment of FU levels in liquid and solid cultures. The present study focused on the impacts of solid-state fermentation (SSF) using solid substrates (wheat, oat, and rice), as well as the effects of fermentation parameters (pH, temperature, and incubation period), on the generation of FU. All the fermentation parameters had significant effects on the synthesis of FU. In a study of 25 ℃, 5.5 pH, and 21 days of incubation period combinations calculated -to give maximal FU production, it was found that the optimal values were 25 ℃, 5.5 pH, and 21 days, respectively. In a solid substrate medium culture, FU could be produced from SSF. At 30 days, a medium composed of rice yielded the most FU (798.50 mg/L), followed by a medium composed of wheat and oats (640.50 and 450.50 mg/L), respectively. An efficient method for increasing FU production on a large scale could be found in this approach. The results of this study might have multiple applications in different industrial fermentation processes.

• Analytical Science and Technology
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• v.11 no.1
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• pp.36-41
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• 1998

A gas chromatography-mass spectrometry method for the determination of 5-fluorourasil in human plasma is described. The method involves a single extraction procedure with 10 ml of isopropanol-ether(20:80) solution and pentafluoro-benzylation. Samples were injected using an automatic injector, followed by separation on a nonpolar capillary column and detection with a mass selective detector(MSD). No endogeneous compounds were found to interfere. The detection limit, based upon an assayed plasma volume of 0.5, was 3 ng/ml. The extraction yield was found to be above 80%. Plasma 5-FU concentrations were determined by this method in about 500 plasma samples from cancer patients undergoing treatment with 5-FU. This method is suitable for monitoring of 5-FU in plasma of cancer patients.

• Journal of Life Science
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• v.22 no.8
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• pp.1018-1023
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• 2012

Snail is a zinc finger transcription factor that induces epithelial-to-mesenchymal transition (EMT), which promotes tumor invasion and metastasis by repressing E-cadherin expression. In addition, Snail restricts the cellular apoptotic response to apoptotic stimuli or survival factor withdrawal; however, its molecular mechanism remains largely unknown. In this study, we have investigated the mechanism underlying Snail-mediated chemoresistance to 5-fluorouracil (5-FU), one of the most widely used anti-cancer drugs. When Snail was overexpressed by doxycycline (DOX) in MCF-7 #5 cells, it inhibited 5-FU-induced apoptotic cell death and switched the cell death mode to necrosis. Snail expression, either by DOX treatment in MCF-7 #5 cells or by the transfection of Snail expression vectors pCR3.1-Snail-Flg, phosphorylation-resistant pCR3.1-S104, and 107A Snail-Flg in MCF-7 cells specifically induced PTEN down-regulation/inactivation and Akt/PKB activation, without affecting ERK1/2 activity. In addition, Snail prominently suppressed 5-FU-induced increases in p53 levels. These findings demonstrate that Snail switches 5-FU-induced apoptosis to necrosis through the activation of Akt/PKB and the down-regulation of p53 levels.

• Nutrition Research and Practice
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• v.9 no.2
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• pp.129-136
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• 2015

BACKGROUND/OBJECTIVES: A variety of immunomodulators can improve the efficacy of low-dose chemotherapeutics. Active hexose correlated compound (AHCC), a mushroom mycelia extract, has been shown to be a strong immunomodulator. Whether AHCC could enhance the antitumor effect of low-dose 5-fluorouracil (5-FU) via regulation of host immunity is unknown. MATERIALS/METHODS: In the current study Hepatoma 22 (H22) tumor-bearing mice were treated with PBS, 5-FU ($10mg{\cdot}kg^{-1}{\cdot}d^{-1}$, i.p), or AHCC ($360mg{\cdot}kg^{-1}{\cdot}d^{-1}$, i.g) plus 5-FU, respectively, for 5 d. $CD^{3+}$, $CD^{4+}$, $CD^{8+}$, and NK in peripheral blood were detected by flow cytometry. ALT, AST, BUN, and Cr levels were measured by biochemical assay. IL-2 and $TNF{\alpha}$ in serum were measured using the RIA kit and apoptosis of tumor was detected by TUNEL staining. Bax, Bcl-2, and TS protein levels were measured by immunohistochemical staining and mRNA level was evaluated by RT-PCR. RESULTS: Diet consumption and body weight showed that AHCC had no apparent toxicity. AHCC could reverse liver injury and myelosuppression induced by 5-FU (P < 0.05). Compared to mice treated with 5-FU, mice treated with AHCC plus 5-FU had higher thymus index, percentages of $CD^{3+}$, $CD^{4+}$, and NK cells (P < 0.01), and ratio of $CD^{4+}$/$CD^{8+}$ (P < 0.01) in peripheral blood. Radioimmunoassay showed that mice treated with AHCC plus 5-FU had the highest serum levels of IL-2 and $TNF{\alpha}$ compared with the vehicle group and 5-FU group. More importantly, the combination of AHCC and 5-FU produced a more potent antitumor effect (P < 0.05) and caused more severe apoptosis in tumor tissue (P < 0.05) compared with the 5-FU group. In addition, the combination of AHCC and 5-FU further up-regulated the expression of Bcl-2 associated X protein (Bax) (P < 0.01), while it down-regulated the expression of B cell lymphoma 2 (Bcl-2) (P < 0.01). CONCLUSIONS: These results support the claim that AHCC might be beneficial for cancer patients receiving chemotherapy.

• YAKHAK HOEJI
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• v.40 no.5
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• pp.532-538
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• 1996

In cancer chemotherapy, it is necessary to control the phamacokinetic behavior of an antitumor drug for effective treatment. Therefore, two 5-fluorouracil derivatives synthesize d with N-a-cyloxycarbonyl derivatives {1-(N-t-butyloxycarbonyl)leucyloxymethyl-5-FU(BLFU) and 1-(N-t-carbobenzyloxymethyl)leucyloxymethyl-5-FU(CLFU)}. prodrugs of 5-fluorouracil, antitumor agent, were loaded into liposome of different lipid compositions. After liposomal drugs were injected intramuscularly, their pharmacokinetics and tissue distribution were assessed. The $AUC_{0{\to}{\infty}$ values were 1.29, 72.50, 85.57, 66.40 and 103.60${\mu}$g.hr/ml for 5-FU, BLFU, CLFU, BLFU- and CLFU-loaded liposome, respectively. 5-FU was distributed to spleen and liver with a maximal concentration after 1 hr and eliminated after 24 hr. But both prodrugs and dimyristoylphosphatidylcholine liposome entrapped prodrugs were distributed to spleen and liver at a lower concentration but maintained for a long time with a relatively high concentration in lung. Especially, liposome-entrapped CLFU was distributed to lung with a maximal concentration after 1 hr and redistributed to spleen increasingly, while the concentration of liposome-entrapped BLFU in lung reached a maximal level after 12 hr.