کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2580969 | 1130167 | 2010 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
A novel anticancer agent, retigeric acid B, displays proliferation inhibition, S phase arrest and apoptosis activation in human prostate cancer cells
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موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
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چکیده انگلیسی
Retigeric acid B (RB), a naturally occurring pentacyclic triterpenic acid, has been noted for its antifungal properties in vitro. Here, we observed that RB inhibited prostate cancer cell proliferation and induced cell death in a dose-dependent manner, but exerted very little inhibitory effect on noncancerous prostate epithelial cell viability. Treatment of androgen-independent PC-3 cells with RB caused a moderate increase in p21Cip1, and enforced the cell cycle arrest in the S phase. A block of S phase was accompanied with decreases in cyclin B, and increases in cyclin E and cyclin A proteins and phosphorylated retinoblastoma protein (pRb), whereas the expression of cdk2 remained almost unchanged in PC-3 cells exposed to RB. Moreover, RB significantly inhibited DNA synthesis with a dose-dependent reduction in the incorporation of BrdU into DNA, and enhanced apoptosis of PC-3 cells with induction of a higher ratio of Bax/Bcl-2 proteins, and activation of caspase-3 which, in turn, promoted the cleavage of poly (ADP-ribose) polymerase (PARP). However, pretreatment with the pan-caspase inhibitor z-VAD-fmk only partially alleviated RB-triggered apoptosis in PC-3 cells, suggesting the involvement of both caspase-dependent and caspase-independent pathways. Additionally, treatment of androgen-sensitive LNCaP cells with RB led to a reduction in the expression of androgen receptor (AR), and subsequently decreased the transactivity of AR. These observations help to support the search for promising candidates to treat prostate cancer.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Chemico-Biological Interactions - Volume 188, Issue 3, 5 December 2010, Pages 598-606
Journal: Chemico-Biological Interactions - Volume 188, Issue 3, 5 December 2010, Pages 598-606
نویسندگان
Han Liu, Yi-qing Liu, Yong-qing Liu, Ai-hui Xu, Charles Y.F. Young, Hui-qing Yuan, Hong-xiang Lou,