کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10770876 | 1050836 | 2005 | 5 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Two glucosylceramide synthase inhibitors attenuate doxorubicin-induced p21Cip1/Waf1 upregulation in HepG2 cells, irrespective of their differential chemosensitizing properties
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله

چکیده انگلیسی
We have previously reported that HepG2 human hepatocarcinoma cells are sensitized to doxorubicin-induced apoptosis by the glucosylceramide synthase inhibitor d,l-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) but not by the more specific inhibitor d,l-threo-1-phenyl-2-hexadecanoylamino-3-pyrrolidino-1-propanol (PPPP). Herein we investigated whether the chemosensitizing action of PDMP impinged on any unspecific effect of this compound on doxorubicin-induced expression of p53 and/or p21Cip1/Waf1, namely two proteins reported to modulate the apoptotic response to DNA-damaging agents, in a positive or negative fashion, respectively. We show that, in HepG2 cells, PDMP did not substantially affect doxorubicin-induced p53 upregulation, whereas drug-evoked upregulation of p21Cip1/Waf1 was markedly attenuated. Although this outcome could be expected to account for the chemosensitizing effect of PDMP, impaired upregulation of p21Cip1/Waf1, in the setting of unaltered p53 expression, was also observed in the case of PPPP. These results, while raising the possibility of a link between attenuation of drug-evoked p21Cip1/Waf1 expression and redirection of (glyco)sphingolipid metabolism, show that, differently from other tumor systems, attenuation of doxorubicin-induced p21Cip1/Waf1 expression is at least not sufficient to sensitize HepG2 cells to the apoptotic action of the drug.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 330, Issue 1, 29 April 2005, Pages 242-246
Journal: Biochemical and Biophysical Research Communications - Volume 330, Issue 1, 29 April 2005, Pages 242-246
نویسندگان
Sabrina Di Bartolomeo, Angelo Spinedi,