کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2581346 1130186 2010 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Morin fosters apoptosis in experimental hepatocellular carcinogenesis model
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Morin fosters apoptosis in experimental hepatocellular carcinogenesis model
چکیده انگلیسی

Here we investigated the in vivo effect of morin (500 ppm in diet) in fostering apoptosis in diethylnitrosamine (DEN) (200 mg/kg bodyweight) mediated experimental hepatocellular carcinogenesis model. We analyzed the expression of cytosolic protein Akt and their important apoptotic downstream targets like caspase-9, Bcl-2, Bax, GSK-3βin vivo, by immunoblot analysis. In silico docking studies indicated that morin could serve as a better inhibitor than the classical PI3K inhibitor LY294002. The results obtained from in vivo studies confirm this. We also demonstrate here that morin's interaction with a defined set of amino acids of PI3K p110γ catalytic subunit resulted in the down-regulation of p-AktSer473, p-AktThr308 and total Akt causing the attenuation of its downstream targets in DEN-induced hepatocellular carcinoma. Further, morin caused the up-regulation of tumor suppressor PTEN, an important negative regulator of Akt, thus initiating apoptosis. Supplementation of morin to experimental animals modulated Bcl-2/Bax ratio causing the release of cyt C and up-regulation of caspase-3 and -9. Morin was also found to prevent the Akt-mediated suppression of GSK-3β possibly causing cell cycle arrest at the G1/S phase. These observations were supported by the DNA fragmentation and transmission electron microscopy results, which showed the occurrence of apoptosis. In conclusion, our findings demonstrate that morin begets apoptosis in DEN-induced hepatocellular carcinoma.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Chemico-Biological Interactions - Volume 183, Issue 2, 27 January 2010, Pages 284–292
نویسندگان
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