کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8435724 | 1546690 | 2014 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Imperatorin induces Mcl-1 degradation to cooperatively trigger Bax translocation and Bak activation to suppress drug-resistant human hepatoma
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موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
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چکیده انگلیسی
Imperatorin is a small molecule nature compound isolated from the root of Angelica dahurica, and has been shown to exhibit multiple bioeffector functions, including anti-cancer activity. However, the molecular mechanism underlying imperatorin in suppression of tumor growth is unknown. In this study, we aimed at elucidating the molecular mechanisms underlying imperatorin function and determining the efficacy of imperatorin in suppression of drug-resistant human liver cancer. We observed that imperatorin suppresses tumor cell growth through inducing apoptosis, and imperatorin is more effective in induction of multidrug-resistant human liver cancer cells in vitro. We further determined that imperatorin induces apoptosis through both extrinsic and intrinsic apoptosis pathway. At the molecular level, we identified Mcl-1 as the molecular target of imperatorin and determined that imperatorin induces protesome-dependent Mcl-1 degradation to release Bak and Bax to trigger apoptosis in liver cancer cells. Consistent with its in vitro apoptosis induction activity, imperatorin exhibited potent activity against multidrug-resistant liver cancer xenograft growth in vivo. Taken together, we determined that imperatorin is a Mcl-1 degradation inducer that can effectively suppress multidrug-resistant human liver cancer growth in vivo, and thus holds great promise for development as an effective small molecule anti-cancer agent in human liver cancer therapy to overcome drug resistance.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cancer Letters - Volume 348, Issues 1â2, 28 Juneâ1 July 2014, Pages 146-155
Journal: Cancer Letters - Volume 348, Issues 1â2, 28 Juneâ1 July 2014, Pages 146-155
نویسندگان
Xia Li, Xueli Zeng, Jianguo Sun, Hua Li, Ping Wu, Kwok-Pui Fung, Feiyan Liu,