Capsaicin Suppresses Cell Proliferation, Induces Cell Cycle Arrest and ROS Production in Bladder Cancer Cells through FOXO3a-Mediated Pathways.

Capsaicin Suppresses Cell Proliferation, Induces Cell Cycle Arrest and ROS Production in Bladder Cancer Cells through FOXO3a-Mediated Pathways.
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DOI:
10.3390/molecules21101406
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发表时间:
2016-10-21
期刊:
Molecules (Basel, Switzerland)
影响因子:
--
通讯作者:
Wang X
Wang X
中科院分区:
其他
文献类型:
--
作者:
Qian K;Wang G;Cao R;Liu T;Qian G;Guan X;Guo Z;Xiao Y;Wang X

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辣椒素 (CAP) 是一种高度选择性的瞬时受体电位香草酸 1 型 (TRPV1) 激动剂,已被广泛报道具有抗氧化、抗炎和抗癌活性。目前,有几种治疗膀胱癌(BCa)的方法可用,但伴随着不利的结果。先前的研究报道了 CAP 预防 BCa 肿瘤发生的潜在临床效果。然而,其潜在的分子机制仍然未知。我们的转录组分析表明 BCa 中钙信号通路、细胞周期调节、ROS 代谢和 FOXO 信号通路之间存在密切联系。在本研究中,进行了多项实验来研究 CAP 对 BCa 细胞(5637 和 T24)和 NOD/SCID 小鼠的影响。我们的结果表明,CAP 可以通过抑制体外和体内增殖来抑制 BCa 肿瘤发生。此外,CAP 诱导细胞周期停滞在 G0/G1 期并产生 ROS。重要的是,我们的研究表明,CAP 治疗后 FOXO3a 显着增加。此外,我们观察到 CAP 没有显着改变细胞凋亡,而过氧化氢酶和 SOD2 显着上调,这可以清除 ROS 并防止细胞死亡。因此,我们的结果表明,CAP 可能通过 FOXO3a 介导的途径抑制 BCa 的活力和肿瘤发生。
Capsaicin (CAP), a highly selective agonist for transient receptor potential vanilloid type 1 (TRPV1), has been widely reported to exhibit anti-oxidant, anti-inflammation and anticancer activities. Currently, several therapeutic approaches for bladder cancer (BCa) are available, but accompanied by unfavorable outcomes. Previous studies reported a potential clinical effect of CAP to prevent BCa tumorigenesis. However, its underlying molecular mechanism still remains unknown. Our transcriptome analysis suggested a close link among calcium signaling pathway, cell cycle regulation, ROS metabolism and FOXO signaling pathway in BCa. In this study, several experiments were performed to investigate the effects of CAP on BCa cells (5637 and T24) and NOD/SCID mice. Our results showed that CAP could suppress BCa tumorigenesis by inhibiting its proliferation both in vitro and in vivo. Moreover, CAP induced cell cycle arrest at G0/G1 phase and ROS production. Importantly, our studies revealed a strong increase of FOXO3a after treatment with CAP. Furthermore, we observed no significant alteration of apoptosis by CAP, whereas Catalase and SOD2 were considerably upregulated, which could clear ROS and protect against cell death. Thus, our results suggested that CAP could inhibit viability and tumorigenesis of BCa possibly via FOXO3a-mediated pathways.
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