Bioactive tanshinones in Salvia miltiorrhiza inhibit the growth of prostate cancer cells in vitro and in mice.
Bioactive tanshinones in Salvia miltiorrhiza inhibit the growth of prostate cancer cells in vitro and in mice.
复制标题
DOI：
10.1002/ijc.25678
复制
发表时间：
2011-09-01
影响因子：
6.4
通讯作者：
Zhou, Jin-Rong
中科院分区：
文献类型：
--
作者：
Gong, Yi;Li, Yanli;Lu, Yin;Li, Linglin;Abdolmaleky, Hamid;Blackburn, George L.;Zhou, Jin-Rong
寻找有效、安全的前列腺癌化学预防和治疗药物已成为研究的重中之重。本研究的目的是确定一组丹参酮，隐丹参酮（CT），丹参酮IIA（T2A）和丹参酮I（T1）对前列腺癌的作用。体外研究表明，丹参酮通过诱导细胞周期阻滞和凋亡，以剂量依赖的方式抑制人前列腺癌细胞株的生长。在三种化合物中，T1的活性最强，IC50约为3 - 6 µ M。另一方面，丹参酮对正常前列腺上皮细胞生长的不良影响要小得多。表观遗传途径聚焦阵列分析确定极光A激酶作为丹参酮作用的可能靶点。Aurora A在前列腺癌细胞系中过表达。此外，敲低前列腺癌细胞中的Aurora A显著降低细胞生长。丹参酮显著下调Aurora A的表达，提示Aurora A可能是丹参酮的作用靶点。丹参酮，特别是T1，也显示出强大的抗血管生成活性在体外和体内。此外，T1抑制小鼠DU 145前列腺肿瘤的生长，与诱导细胞凋亡、减少增殖、抑制血管生成和下调Aurora A相关，而不改变食物摄入量或体重。我们的研究结果支持T1可能是一种有效和安全的化学预防或治疗剂对前列腺癌的进展。
Searching for efficacious and safe agents for the chemoprevention and therapy of prostate cancer has become the top priority of research. The objective of this study was to determine the effects of a group of tanshinones from a Chinese herb Salvia Miltiorrhiza, cryptotanshinone (CT), tanshinone IIA (T2A) and tanshinone I (T1) on prostate cancer. The in vitro studies showed that these tanshinones inhibited the growth of human prostate cancer cell lines in a dose-dependent manner via cell cycle arrest and apoptosis induction. Among three compounds, T1 had the most potent activity with IC50s around 3–6µM. On the other hand, tanshinones had much less adverse effects on the growth of normal prostate epithelial cells. The epigenetic pathway focused array assay identified Aurora A kinase as a possible target of tanshinone actions. The expression of Aurora A was overexpressed in prostate cancer cell lines. Moreover, knockdown of Aurora A in prostate cancer cells significantly decreased cell growth. Tanshinones significantly down-regulated the Aurora A expression, suggesting Aurora A may be a functional target of tanshinones. Tanshinones, especially T1, also showed potent anti-angiogenesis activity in vitro and in vivo. Furthermore, T1 inhibited the growth of DU145 prostate tumor in mice associated with induction of apoptosis, decrease of proliferation, inhibition of angiogenesis and downregulation of Aurora A, whereas it did not alter food intake or body weight. Our results support that T1 may be an efficacious and safe chemopreventive or therapeutic agent against prostate cancer progression.
登录
查看更多内容
影响因子：
11.2
作者：
Hata, T;Furukawa, T;Horii, A
通讯作者：
Horii, A
影响因子：
5.7
作者：
Dar AA;Goff LW;Majid S;Berlin J;El-Rifai W
通讯作者：
El-Rifai W
影响因子：
64.5
作者：
Hirota, T;Kunitoku, N;Saya, H
通讯作者：
Saya, H
影响因子：
4.3
作者：
Lee, W. Y. W.;Chiu, L. C. M.;Yeung, J. H. K.
通讯作者：
Yeung, J. H. K.
影响因子：
56.9
作者：
Kimura, K;Hirano, M;Hirano, T
通讯作者：
Hirano, T