College of Oriental Medicine, Kyung Hee University, Seoul, 130-701, Republic of Korea.
Phytother Res. 2012 May;26(5):669-74. doi: 10.1002/ptr.3616. Epub 2011 Oct 13.
Our group previously reported that tanshinone IIA induced apoptosis via a mitochondria dependent pathway in LNCaP prostate cancer cells. In the present study, the roles of androgen receptor (AR) and p53 signaling pathways were investigated in tanshinone IIA-induced G1 arrest in LNCaP cells. Tanshinone IIA significantly inhibited the growth and proliferation of LNCaP cells by colony formation and BrdU incorporation assays, respectively. Tanshinone IIA induced cell cycle arrest at G1 phase and down-regulated cyclin D1, CDK2 and CDK4. Furthermore, tanshinone IIA activated the phosphorylation of p53 at Ser 15 residue and its downstream p21 and p27. Additionally, tanshinone IIA suppressed the expression of AR and prostate specific antigen (PSA). Conversely, silencing p53 using its specific siRNA reversed cyclin D1 expression inhibited by tanshinone IIA. However, knockdown of AR had no effect on the p53/p21/p27 signaling pathway activated by tanshinone IIA in LNCaP cells. In AR siRNA-transfected cells, tanshinone IIA did not cause cell cycle arrest and reduce cyclin D1, implying that AR is essential to induce G1 arrest by tanshinone IIA in LNCaP cells. Taken together, the findings suggest that tanshinone IIA induces G1 arrest via activation of p53 signaling and inhibition of AR in LNCaP cells.
我们的小组之前曾报道过丹参酮 IIA 通过依赖线粒体的途径诱导 LNCaP 前列腺癌细胞凋亡。在本研究中，我们研究了在丹参酮 IIA 诱导 LNCaP 细胞 G1 期阻滞中，雄激素受体 (AR) 和 p53 信号通路的作用。丹参酮 IIA 通过集落形成和 BrdU 掺入试验分别显著抑制 LNCaP 细胞的生长和增殖。丹参酮 IIA 诱导细胞周期停滞在 G1 期，并下调细胞周期蛋白 D1、CDK2 和 CDK4。此外，丹参酮 IIA 激活了 p53 在 Ser15 残基上的磷酸化及其下游的 p21 和 p27。此外，丹参酮 IIA 抑制了 AR 和前列腺特异性抗原 (PSA) 的表达。相反，使用其特异性 siRNA 沉默 p53 可逆转丹参酮 IIA 抑制的 cyclin D1 表达。然而，AR 的敲低对丹参酮 IIA 在 LNCaP 细胞中激活的 p53/p21/p27 信号通路没有影响。在 AR siRNA 转染的细胞中，丹参酮 IIA 不会引起细胞周期停滞和降低 cyclin D1，表明 AR 对于丹参酮 IIA 在 LNCaP 细胞中诱导 G1 期阻滞是必需的。综上所述，这些发现表明丹参酮 IIA 通过激活 p53 信号通路和抑制 AR 在 LNCaP 细胞中诱导 G1 期阻滞。
