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991.
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A novel microtubule depolymerizing colchicine analogue triggers apoptosis and autophagy in HCT‐116 colon cancer cells 下载免费PDF全文
Ashok Kumar Baljinder Singh Parduman R. Sharma Sandip B. Bharate Ajit K. Saxena D. M. Mondhe 《Cell biochemistry and function》2016,34(2):69-81
Colchicine is a tubulin‐binding natural product isolated from Colchicum autumnale. Here we report the in vitro anticancer activity of C‐ring modified semi‐synthetic derivative of colchicine; N‐[(7S)‐1,2,3‐trimethoxy‐9‐oxo‐10‐(4‐phenyl‐piperidin‐1‐yl)‐5,6,7,9 tetrahydrobenzo[a]heptalen‐7‐yl]acetamide ( 4h ) on colon cancer HCT‐116 cell line. The compound 4h was screened for anti‐proliferative activity against different human cancer cell lines and was found to exhibit higher cytotoxicity against colon cancer cell lines HCT‐116 and Colo‐205 with IC50 of 1 and 0.8 μM respectively. Cytotoxicity of the compound to the normal fR2 breast epithelial cells and normal HEK293 human embryonic kidney cells was evaluated in concentration and time‐dependent manner to estimate its selectivity for cancer cells which showed much better selectivity than that of colchicine. Compound 4h induced cell death in HCT‐116 cells by activating apoptosis and autophagy pathways. Autophagy inhibitor 3‐MA blocked the production of LC3‐II and reduced the cytotoxicity in response to 4h , but did not affect apoptosis, suggesting thereby that these two were independent events. Reactive oxygen species scavenger ascorbic acid pretreatment not only decreased the reactive oxygen species level but also reversed 4h induced cytotoxicity. Treatment with compound 4h depolymerized microtubules and the majority of cells arrested at the G2/M transition. Together, these data suggest that 4h has better selectivity and is a microtubule depolymerizer, which activates dual cell‐death machineries, and thus, it could be a potential novel therapeutic agent in cancer therapy. Copyright © 2016 John Wiley & Sons, Ltd. 相似文献
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The trend of increasing height can be interpreted as a reflection of the unfolding progress of civilization. Height changes among children and adolescents are good markers of this trend. We analyze the secular trend in the heights of children and adolescents in the Czech Republic on the basis of data from anthropological surveys. The earliest height data pertain to Czech youths who attended the Military Schools in Austria in 1800-1809. Data also exist for 1895 and continue in 1951 and at 10-year intervals thereafter. Growth curves were obtained for separate age groups by fitting mean values via third-order polynomial smoothing splines. Between 1951 and 2001, the mean heights of boys and girls aged 2.5 years increased by 2.7 and 3 cm, respectively. Since 1895, the mean height of 13-year-old boys has increased by 19.4 cm, and the mean height of girls has increased by 18.3 cm. 相似文献
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1 Introduction Molluscan species exhibit a range of morphologies associated with their particular function and habitat. The razor clam (Ensis siliqua) is a bivalve mollusc, usually found in fine sands, that burrows up to depths of 20 fathoms (~36 m)[1]. The species is found in several coastal regions of the British Isles, the Norwegian Sea, the Baltic south, the Iberian Peninsula, the Mediterranean and along the Atlantic coast of Morrocco[2]. The protec- tive outer shell, which is often … 相似文献
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Serum levels of immunoglobulins G, A, M, and E (IgG, IgA, IgM, and IgE, respectively); allergenspecific IgE antibodies; and interleukin-4 (IL-4) were measured in ten cosmonauts before and after flights of 7–11 days on the International Space Station. These relatively short spaceflights did not cause any significant changes in the parameters tested. No linear correlation was found between the serum levels of total IgE and IL-4 for either the pre-or the postflight period. 相似文献
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Continuous wavelet analysis can be used to quantitatively describe local changes in cardiac rhythm oscillations. The following new indices of the wave structure of the cardiac rhythm were suggested: the rate of changes in the frequency of the oscillatory component within a given time interval, the lengths of the fading periods for specific frequency oscillations detected on the cardiointervalogram, and the changes in the instantaneous frequency-amplitude ratios during the observation period. These indices allow a deeper insight into sympathetic and parasympathetic oscillators that affect the cardiac rhythm. 相似文献
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M. A. Abdurakhmanov I. D. Stolyarov A. G. Il’vesa T. L. Tsvetkova V. V. Lebedev 《Human physiology》2006,32(2):154-156
The relationship between the parameters of the distribution of plantar pressure and the state of a patient with multiple sclerosis has been studied with repeated measurements, before and after (or during) treatment. The possibility of using this method for study of walking function impairment in a chronic demyelinating process is considered. 相似文献