• Title/Summary/Keyword: acidic induction

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Induction of Autophagy by Low Dose of Cisplatin in H460 Lung Cancer Cells (폐암세포주에서 저용량 시스플라틴에 의해 유도된 자가포식)

  • Shin, Jeong-Hyun;Jang, Hye-Yeon;Chung, Jin-Soo;Cho, Kyung-Hwa;Hwang, Ki-Eun;Kim, So-Young;Kim, Hui-Jung;Lee, Sam-Youn;Lee, Mi-Kung;Park, Soon-Ah;Moon, Sun-Rock;Lee, Kang-Kyu;Jo, Hyang-Jeong;Yang, Sei-Hoon
    • Tuberculosis and Respiratory Diseases
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    • v.69 no.1
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    • pp.16-23
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    • 2010
  • Background: Most lung cancer patients receive systemic chemotherapy at an advanced stage disease. Cisplatin-based chemotherapy is the main regimen for treating advanced lung cancer. Recently, autophagy has become an important mechanism of cellular adaptation under starvation or cell oxidative stress. The purpose of this study was to determine whether or not autophagy can occurred in cisplatin-treated lung cancer cells. Methods: H460 cells were incubated with RPMI 1640 and treated in $5{\mu}M$ or $20{\mu}M$ cisplatin concentrations at specific time intervals. Cells surviving cisplatin treatment were measured and compared using an MTT cell viability assay to cells that underwent apoptosis with autophagy by nuclear staining, apoptotic or autophagic related proteins, and autophagic vacuoles. The development of acidic vascular organelles was using acridine orange staining and fluorescent expression of GFP-LC3 protein in its transfected cells was observed to evaluate autophagy. Results: Lung cancer cells treated with $5{\mu}M$ cisplatin-treated were less sensitive to cell death than $20{\mu}M$ cisplatin-treated cells in a time-dependent manner. Nuclear fragmentation at $5{\mu}M$ was not detected, even though it was discovered at $20{\mu}M$. Poly (ADP-ribose) polymerase cleavages were not detected in $5{\mu}M$ within 24 hours. Massive vacuolization in the cytoplasm of $5{\mu}M$ treated cells were observed. Acridine orange stain-positive cells was increased according in time-dependence manner. The autophagosome-incorporated LC3 II protein expression was increased in $5{\mu}M$ treated cells, but was not detected in $20{\mu}M$ treated cells. The expression of GFP-LC3 were increased in $5{\mu}M$ treated cells in a time-dependent manner. Conclusion: The induction of autophagy occurred in $5{\mu}M$ dose of cisplatin-treated lung cancer cells.

The Expression of Oncogenes on the Radiation-induced Apoptosis in SCK Mammary Adenocarcinoma Cell Line (SCK 선암세포주에서 방사선 조사에 의해 유도되는 Apoptosis에 미치는 암유전자의 발현)

  • Lee Hyung Sik;Park Hong Kyu;Moon Chang Woo;Yoon Seon Min;Hur Won Joo;Jeong Su Jin;Jeong Min Ho;Lee Sang Hwa
    • Radiation Oncology Journal
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    • v.17 no.1
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    • pp.70-77
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    • 1999
  • Purpose : The expression of p53, P211WAF/CIP, Bcl-2, and Bax underlying the radiation-induced apoptosis in different pH environments using SCK mammary adenocarcinoma cell line was investigated. Materials and Methods Mammary adenocarcinoma cells of hi) mice (SCK cells) in exponential growth phase were irradiated with a linear accelerator at room temperature. The cells were irradiated with 12 Gy and one hour later, the media was replaced with fresh media at a different pHs. After Incubation at 37Microbioiogy, College of Medicine Dong A University for 0$\~$48 h, the extort of apoptosis was determined using agarose gel electrophoresis and flow cytometry. The progression of cells through the cell cycle after irradiation in different pHs was also determined with flow cytometry. Western blot analysis was used to monitor p53, p211WAFfCIP, Bcl-2, and Bu protein levels. Results : The induction of apoptosis by irradiation in pH 6.6 medium was markedly less than that in pH 7.5 medium. The radiation-induced G2IM arrest in pH 6.6 medium lasted markedly longer than that in pH 7.5 medium. Considerable amounts of p53 and p21 proteins already existed at pH 7.5 and increased the level of p53 and p21 significantly after 12 Gy X-irradiation. An incubation at pH 6.6 after 12 Gy X-irradiation did not change the level of p53 and p21 protein levels significantly. Bcl-2 proteins were not significantly affected by radiation and showed no correlation with cell susceptibility to radiation-induced apoptosis in different pHs. An exposure to 12 Gy of X-rays increased the level of Bax protein at pH 7.5 but at pH 6.6, it was slight. Conclusions : The molecular mechanism underlying radiation-induced apoptosis in dinerent pH environments using SCK mammary adenocarcinoma cell line was dependent of the expression p53 and P211YVAF/CIP proteins. We may propose following hypothesis that an acidic stress augments the radiation-induced G2iM arrest, which inhibiting the irradiated cells undergo post-mitotic apoptosis. The effects of environmental acidity on anti-apoptotic and pro-apoptotic function of Bcl-2 family was unclear in SCK mammary adenocarcinoma cell line.

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The Comparative Understanding between Red Ginseng and White Ginsengs, Processed Ginsengs (Panax ginseng C. A. Meyer) (홍삼과 백삼의 비교 고찰)

  • Nam, Ki-Yeul
    • Journal of Ginseng Research
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    • v.29 no.1
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    • pp.1-18
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    • 2005
  • Ginseng Radix, the root of Panax ginseng C. A. Meyer has been used in Eastern Asia for 2000 years as a tonic and restorative, promoting health and longevity. Two varieties are commercially available: white ginseng(Ginseng Radix Alba) is produced by air-drying the root, while red ginseng(Ginseng Radix Rubra) is produced by steaming the root followed by drying. These two varieties of different processing have somewhat differences by heat processing between them. During the heat processing for preparing red ginseng, it has been found to exhibit inactivation of catabolic enzymes, thereby preventing deterioration of ginseng quality and the increased antioxidant-like substances which inhibit lipid peroxide formation, and also good gastro-intestinal absorption by gelatinization of starch. Moreover, studies of changes in ginsenosides composition due to different processing of ginseng roots have been undertaken. The results obtained showed that red ginseng differ from white ginseng due to the lack of acidic malonyl-ginsenosides. The heating procedure in red ginseng was proved to degrade the thermally unstable malonyl-ginsenoside into corresponding netural ginsenosides. Also the steaming process of red ginseng causes degradation or transformation of neutral ginsenosides. Ginsenosides $Rh_2,\;Rh_4,\;Rs_3,\;Rs_4\;and\;Rg_5$, found only in red ginseng, have been known to be hydrolyzed products derived from original saponin by heat processing, responsible for inhibitory effects on the growth of cancer cells through the induction of apoptosis. 20(S)-ginsenoside $Rg_3$ was also formed in red ginseng and was shown to exhibit vasorelaxation properties, antimetastatic activities, and anti-platelet aggregation activity. Recently, steamed red ginseng at high temperature was shown to provide enhance the yield of ginsenosides $Rg_3\;and\;Rg_5$ characteristic of red ginseng Additionally, one of non-saponin constituents, panaxytriol, was found to be structually transformed from polyacetylenic alcohol(panaxydol) showing cytotoxicity during the preparation of red ginseng and also maltol, antioxidant maillard product, from maltose and arginyl-fructosyl-glucose, amino acid derivative, from arginine and maltose. In regard to the in vitro and in vivo comparative biological activities, red ginseng was reported to show more potent activities on the antioxidant effect, anticarcinogenic effect and ameliorative effect on blood circulation than those of white ginseng. In oriental medicine, the ability of red ginseng to supplement the vacancy(허) was known to be relatively stronger than that of white ginseng, but very few are known on its comparative clinical studies. Further investigation on the preclinical and clinical experiments are needed to show the differences of indications and efficacies between red and white ginsengs on the basis of oriental medicines.