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Gilda Grard Joseph N. Fair Deanna Lee Elizabeth Slikas Imke Steffen Jean-Jacques Muyembe Taylor Sittler Narayanan Veeraraghavan J. Graham Ruby Chunlin Wang Maria Makuwa Prime Mulembakani Robert B. Tesh Jonna Mazet Anne W. Rimoin Travis Taylor Bradley S. Schneider Graham Simmons Eric Delwart Nathan D. Wolfe Charles Y. Chiu Eric M. Leroy 《PLoS pathogens》2016,12(3)
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B S Vinod J Antony H H Nair V T Puliyappadamba M Saikia S Shyam Narayanan A Bevin R John Anto 《Cell death & disease》2013,4(2):e505
5-Fluorouracil (5-FU) is the first rationally designed antimetabolite, which achieves its therapeutic efficacy through inhibition of the enzyme thymidylate synthase (TS), which is essential for the synthesis and repair of DNA. However, prolonged exposure to 5-FU induces TS overexpression, which leads to 5-FU resistance in cancer cells. Several studies have identified curcumin as a potent chemosensitizer against chemoresistance induced by various chemotherapeutic drugs. In this study, we report for the first time, with mechanism-based evidences, that curcumin can effectively chemosensitize breast cancer cells to 5-FU, thereby reducing the toxicity and drug resistance. We found that 10 μM 5-FU and 10 μM curcumin induces a synergistic cytotoxic effect in different breast cancer cells, independent of their receptor status, through the enhancement of apoptosis. Curcumin was found to sensitize the breast cancer cells to 5-FU through TS-dependent downregulation of nuclear factor-κB (NF-κB), and this observation was confirmed by silencing TS and inactivating NF-κB, both of which reduced the chemosensitizing efficacy of curcumin. Silencing of TS suppressed 5-FU-induced NF-κB activation, whereas inactivation of NF-κB did not affect 5-FU-induced TS upregulation, confirming that TS is upstream of NF-κB and regulates the activation of NF-κB in 5-FU-induced signaling pathway. Although Akt/PI3kinase and mitogen-activated protein kinase pathways are activated by 5-FU and downregulated by curcumin, they do not have any role in regulating the synergism. As curcumin is a pharmacologically safe and cost-effective compound, its use in combination with 5-FU may improve the therapeutic index of 5-FU, if corroborated by in vivo studies and clinical trials. 相似文献
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The influence of epidermal growth factor on DNA and protein synthesis by human gingival fibroblasts was studied. Synchronized cells treated with epidermal growth factor synthesized considerably greater amounts of DNA relative to 10% fetal calf serum and the peak of synthesis ocurred 6 h later than with serum. Epidermal growth factor caused a dose-dependent stimulation of protein synthesis (proline incorporation). Collagen synthesis remained unaffected and, as a result, the proportion of collagen synthesized decreased with increasing epidermal growth factor concentration. Aspirin and indomethacin did not abrogate these effects, indicating that prostaglandins may not be involved. 相似文献
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Three mutants of Impatiens sultani (named as ‘Orange', ‘Crimson', and ‘Pink') show an unusually wide spectrum of aberrations in microsporogenesis. These aberrations range from premeiotic cytomixis to meiotic and postmeiotic irregularities such as precocious disjunction, tripolar separation of chromosomes, chromosome bridges, various patterns of atypical cytokinesis, supernumerary divisions of the meiotic products, and irregular divisions in the microspore. As a result of these abnormalities Orange is partially and Crimson and Pink are completely pollen sterile. The stigmas of Pink, besides, do not support pollen germination. The failure of pollen germination is attributed to the defective stigmatic fluid of Pink, which, compared to that of Orange and Crimson lacks organic compounds absorbing UV light at 261 nm. This constitutive deficiency in stigmatic fluid appears to be a little investigated facet of female sterility. 相似文献
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