• Title/Summary/Keyword: FAS Activity

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Pulsed Electromagnetic Field Enhances Doxorubicin-induced Reduction in the Viability of MCF-7 Breast Cancer Cells (맥동 전자기장 처리에 의한 독소루비신 유도 유방암 세포 생존저하 촉진)

  • Sung-Hun WOO;Yoon Suk KIM
    • Korean Journal of Clinical Laboratory Science
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    • v.56 no.1
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    • pp.73-84
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    • 2024
  • A pulsed electromagnetic field (PEMF) enhances the efficacy of several anticancer drugs. Doxorubicin (DOX) is an anticancer agent used to treat various malignancies, including breast cancer. This study examined whether a PEMF increases the anticancer effect of DOX on MCF-7 human breast cancer cells and elucidated the underlying mechanisms affected by PEMF stimulation in DOX-treated MCF-7 human breast cancer cells. A cotreatment with DOX and a PEMF potentiated the reduction in MCF-7 cell viability compared to the treatment with DOX alone. The PEMF elevated DOX-induced G1 arrest by affecting cyclin-dependent kinase 2 phosphorylation and the expression of G1 arrest-related molecules, including p53, p21, cyclin E2, and polo like kinase 1. In addition, PEMF increased the DOX-induced upregulation of proapoptotic proteins, such as Fas and Bcl-2-associated X, and the downregulation of antiapoptotic proteins, including myeloid leukemia 1 and survivin. PEMF promoted the DOX-induced activation of caspases-8, -9, and -7 and poly (adenosine diphosphate-ribose) polymerase cleavage in MCF-7 cells. In conclusion, PEMF enhances the anticancer activity in DOX-treated MCF-7 breast cancer cells by increasing G1 cell cycle arrest and caspase-dependent apoptosis. These findings highlight the potential use of a PEMF as an adjuvant treatment for DOX-based chemotherapy against breast cancer.

Effect of Grape Seed Water Extract on Lipid Metabolism and Erythrocyte Antioxidant Defense System in High-Fat Diet-Induced Obese C57BL/6 Mice (포도씨열수추출물이 고지방식이로 유도한 비만마우스의 지질대사와 적혈구 항산화 방어계에 미치는 영향)

  • Cho, Young-Sook;Jang, Eun-Mi;Jang, Sun-Mi;Chun, Mi-Sun;Shon, Mi-Yae;Kim, Myung-Joo;Lee, Mi-Kyung
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.36 no.12
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    • pp.1537-1543
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    • 2007
  • This study was investigate the effect of grape seed water extract (GSW) on lipid profiles, lipid metabolism and erythrocyte antioxidant defense system in high-fat diet-induced obese mice. Three groups of male C57BL/6 mice were fed different diets for 6 weeks: normal diet (Normal), high-fat diet (HF control; 37% calorie from fat) and high-fat diet supplemented with GSW (HF-GSW; 1% wt/wt). Supplementation of GSW did not affect the body weight, food intake, daily energy intake, white adipose tissue weights and plasma leptin level in high-fat fed mice. Plasma and hepatic cholesterol and triglyceride contents were significantly higher in the HF control group than in the Normal group; however, GSW supplement significantly lowered plasma triglyceride and hepatic cholesterol concentrations compared to the HF control group. GSW supplement significantly increased fecal excretion of triglyceride in high-fat fed mice. Hepatic carnitine palmitoyl transferase activity was significantly higher in the HF-GSW group than in the HF control group, while fatty acid ${\beta}$-oxidation tended to be lowered by GSW supplement. Erythrocyte superoxide dismutase activity was also significantly higher in the HF-GSW group than in the HF control group and glutathione peroxidase activity tended to be lowered in HF-GSW group. The GSW supplement significantly lowered erythrocyte lipid peroxidation level compared to the HF control group. Accordingly, these results suggest that GSW can be considered as a lipid-lowering agent and as being effective for enhancing erythrocyte antioxidant defense system in high-fat diet-induced obese mice.

THE ANTICANCER EFFECT OF PACLITAXEL($Taxol^{(R)}$) IN ORAL SQUAMOUS CELL CARCINOMA XENOGRAFT (이종 이식된 구강편평세포 암종에서 Paclitaxel ($Taxol^{(R)}$)의 항암 효과)

  • Kim, Ki-Hwan;Kim, Chul-Hwan;Han, Se-Jin;Lee, Jae-Hoon
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.28 no.2
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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.

The effects of Allomyrina dichotoma larval extract on palmitate-induced insulin resistance in skeletal muscle cells (장수풍뎅이 유충 추출물이 고지방산 처리 골격근세포의 인슐린 저항성에 미치는 영향)

  • Kim, Kyong;Sim, Mi-Seong;Kwak, Min-Kyu;Jang, Se-Eun;Oh, Yoon Sin
    • Journal of Nutrition and Health
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    • v.55 no.4
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    • pp.462-475
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    • 2022
  • Purpose: Allomyrina dichotoma larvae are one of the approved edible insects with nutritional value and various functional and medicinal properties. Previously we have demonstrated that the Allomyrina dichotoma larval extract (ADLE) ameliorates hepatic insulin resistance in high-fat diet (HFD)-induced diabetic mice through the activation of adenosine monophosphate-activated protein kinase (AMPK). This study investigated the effects of ADLE on insulin resistance in the skeletal muscle and explored mechanisms for enhancing the glucose uptake in palmitate (PAL)-treated C2C12 myotubes. Methods: To induce insulin resistance, the differentiated C2C12 myotubes were treated with PAL (0.5 mM) for 24 hours, and then treated with a 0.5 mg/ml concentration of ADLE, and the resultant effects were measured. The expression levels of glucose transporter-4 (GLUT4), AMPK, and the mitochondrial metabolism-related proteins were analyzed by western blotting. The mRNA expression levels of lipogenesis- related genes were determined by quantitative reverse-transcriptase PCR. Results: The exposure of C2C12 myotubes to 0.5 mg/ml of ADLE increased cell viability significantly compared to PAL-treated cells. ADLE upregulated the protein expression of GLUT4 and enhanced glucose uptake in the PAL-treated cells. ADLE increased the phosphorylated AMPK in both the PAL-treated C2C12 myotubes and HFD-treated skeletal muscle. The reduced expression levels of peroxisome-proliferator-activated receptor gamma co-activator-1 alpha (PGC1α) and uncoupling protein 3 (UCP3) due to the PAL and HFD treatment were reversed by the ADLE treatment. The citrate synthase activity was also significantly increased with the PAL and ADLE co-treatment. Moreover, the mRNA and protein expressions of fatty acid synthesis-related factors were reduced in the PAL and HFD-treated muscle cells, and this effect was significantly attenuated by the ADLE treatment. Conclusion: ADLE activates AMPK, which in turn induces mitochondrial metabolism and reduces fatty acid synthesis in C2C12 myotubes. Therefore, ADLE could be useful for preventing or treating insulin resistance of skeletal muscles in diabetes.

Apoptotic Effect of Proso Millet Grains on Human Breast Cancer MDA-MB-231Cells Is Exerted by Activation of BAK and BAX, and Mitochondrial Damage-mediated Caspase Cascade Activation (기장 종자 유래 추출물의 인간 유방암 MDA-MB-231 세포에 대한 세포독성에 관련된 미토콘드리아 손상-의존적 아폽토시스 유도 효과)

  • Do Youn Jun;Cho Rong Han;Young Ho Kim
    • Journal of Life Science
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    • v.33 no.1
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    • pp.15-24
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    • 2023
  • To examine the antitumor effect of proso millet grains, whether proso millet grains exert apoptotic activity against human cancer cells was investigated. When the cytotoxicity of 80% ethanol (EtOH) extract of proso millet grains was tested against various cancer cells using MTT assay, more potent cytotoxicity was observed against human breast cancer MDA-MB-231 cells than against other cancer cells. When the EtOH extract was evaporated to dryness, dissolved in water, and then further fractionated by sequential extraction using four organic solvents (n-hexane, methylene chloride, ethyl acetate, and n-butanol), the BuOH fraction exhibited the highest cytotoxicity against MDA-MB-231 cells. Along with the cytotoxicity, TUNEL-positive apoptotic nucleosomal DNA fragmentation and several apoptotic responses including BAK/BAX activation, mitochondria membrane potential (Δψm) loss, mitochondrial cytochrome c release into the cytosol, activation of caspase-8/-9/-3, and degradation of poly (ADP-ribose) polymerase (PARP) were detected. However, human normal mammary epithelial MCF-10A cells exhibited a significantly lesser extent of sensitivity compared to malignant MDA-MB-231 cells. Irrespective of Fas-associated death domain (FADD)-deficiency or caspase-8-deficiency, human T acute lymphoblastic leukemia Jurkat cells displayed similar sensitivities to the cytotoxicity of BuOH fraction, excluding an involvement of extrinsic apoptotic mechanism in the apoptosis induction. These results demonstrate that the cytotoxicity of BuOH fraction from proso millet grains against human breast cancer MDA-MB-231 cells is attributable to intrinsic apoptotic cell death resulting from BAK/BAX activation, and subsequent mediation of mitochondrial damage-dependent activation of caspase cascade.