Safrana l Prevents Prostate Cancer Recurrence by Blocking the Re-activation of Quiescent Cancer Cells via Downregulation of S-Phase Kinase-Associated Protein 2.
Safrana l Prevents Prostate Cancer Recurrence by Blocking the Re-activation of Quiescent Cancer Cells via Downregulation of S-Phase Kinase-Associated Protein 2.
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Safrana l 通过下调 S 相激酶相关蛋白 2 来阻止静止癌细胞的重新激活，从而预防前列腺癌复发。
DOI：
10.3389/fcell.2020.598620
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发表时间：
2020
影响因子：
5.5
通讯作者：
Xu HX
中科院分区：
文献类型：
--
作者：
Jiang X;Li Y;Feng JL;Nik Nabil WN;Wu R;Lu Y;Liu H;Xi ZC;Xu HX
静止癌细胞的再增殖被认为是前列腺癌（Pca）复发和进展的主要因素。在这项研究中，我们研究了番红花醛，从番红花（番红花）分离的单萜醛，在体外和体内对静止的Pca细胞再增殖的抑制作用。结果表明，番红花醛通过下调G 0/G1期细胞周期调节蛋白CDK 2、CDK 4、CDK 6和丝氨酸807/811处的磷酸化Rb，并升高细胞周期蛋白依赖性激酶抑制剂p21和p27的水平，有效地阻断了静止Pca细胞的再激活。进一步的机制研究表明，番红花醛抑制Skp 2的mRNA和蛋白表达水平，可能是通过下调两个主要转录因子E2 F1和NF-κB亚基的转录活性。此外，番红花醛抑制AKT在Ser 473处的磷酸化，并解除经典和非经典NF-κB信号通路的调节。番红花醛抑制体内静止的Pca细胞异种移植物的肿瘤生长。此外，番红花醛处理的肿瘤组织显示Skp 2、E2 F1、NF-κB p65、p-IκBα（Ser 32）、c-MYC、p-Rb（Ser 807）、CDK 4、CDK 6和CDK 2减少，而p27和p21蛋白水平升高。因此，我们的研究结果表明，番红花醛在体外和体内抑制静止的Pca细胞的细胞周期重新进入，通过抑制Skp 2的两个主要的转录激活因子，即E2 F1和NF-κB的转录活性，通过下调AKT磷酸化和NF-κB信号通路，分别。
The re-proliferation of quiescent cancer cells is considered to be the primary contributor to prostate cancer (Pca) recurrence and progression. In this study, we investigated the inhibitory effect of safranal, a monoterpene aldehyde isolated from Crocus sativus (saffron), on the re-proliferation of quiescent Pca cells in vitro and in vivo. The results showed that safranal efficiently blocked the re-activation of quiescent Pca cells by downregulating the G0/G1 cell cycle regulatory proteins CDK2, CDK4, CDK6, and phospho-Rb at Ser807/811 and elevating the levels of cyclin-dependent kinase inhibitors, p21 and p27. Further investigation on the underlying mechanisms revealed that safranal suppressed the mRNA and protein expression levels of Skp2, possibly through the deregulation of the transcriptional activity of two major transcriptional factors, E2F1 and NF-κB subunits. Moreover, safranal inhibited AKT phosphorylation at Ser473 and deregulated both canonical and non-canonical NF-κB signaling pathways. Safranal suppressed the tumor growth of quiescent Pca cell xenografts in vivo. Furthermore, safranal-treated tumor tissues exhibited a reduction in Skp2, E2F1, NF-κB p65, p-IκBα (Ser32), c-MYC, p-Rb (Ser807), CDK4, CDK6, and CDK2 and an elevation of p27 and p21 protein levels. Therefore, our findings demonstrate that safranal suppresses cell cycle re-entry of quiescent Pca cells in vitro and in vivo plausibly by repressing the transcriptional activity of two major transcriptional activators of Skp2, namely, E2F1 and NF-κB, through the downregulation of AKT phosphorylation and NF-κB signaling pathways, respectively.
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DOI：
10.4103/0970-1591.117278
发表时间：
2013-07
期刊：
Indian journal of urology : IJU : journal of the Urological Society of India
影响因子：
--
作者：
Samarghandian S;Shabestari MM
通讯作者：
Shabestari MM
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
17.1
作者：
Krall JA;Reinhardt F;Mercury OA;Pattabiraman DR;Brooks MW;Dougan M;Lambert AW;Bierie B;Ploegh HL;Dougan SK;Weinberg RA
通讯作者：
Weinberg RA
影响因子：
64.8
作者：
Bashir, T;Dorrello, NV;Pagano, M
通讯作者：
Pagano, M
影响因子：
4.3
作者：
Geromichalos, George D.;Papadopoulos, Theophanis;Sinakos, Zacharias
通讯作者：
Sinakos, Zacharias