Capsaicin mediates cell cycle arrest and apoptosis in human colon cancer cells via stabilizing and activating p53.
Capsaicin mediates cell cycle arrest and apoptosis in human colon cancer cells via stabilizing and activating p53.
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DOI：
10.7150/ijbs.7730
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发表时间：
2014
影响因子：
9.2
通讯作者：
Jiang H
中科院分区：
文献类型：
--
作者：
Jin J;Lin G;Huang H;Xu D;Yu H;Ma X;Zhu L;Ma D;Jiang H
辣椒素是世界上广泛消费的红辣椒的主要辛辣成分。辣椒素除了具有较强的止痛作用外，还在多种肿瘤模型中发挥了抗肿瘤活性。在此，我们报道了辣椒素通过诱导细胞周期G0/G1期停滞和细胞凋亡而对人结肠癌细胞具有显著的抗增殖作用，这与p21、Bax和裂解PARP的增加有关。辣椒素的抗肿瘤作用机制主要是通过稳定和激活P53来实现的。辣椒素显著延长了P53的半衰期，并显著提高了P53的转录活性。辣椒素通过抑制P53与MDM2之间的相互作用，显著降低MDM2介导的P53泛素化，从而稳定和积聚P53。P53-shRNA实验进一步证明，P53基因敲除后细胞对辣椒素的敏感性显著降低，G0/G1期阻滞，辣椒素诱导的细胞凋亡也明显减少，提示P53在辣椒素的抗肿瘤作用中起着重要作用。总而言之，我们的数据表明，辣椒素或类似物可能在人类结肠癌的治疗中发挥作用。
Capsaicin is the major pungent ingredient in red peppers which is world widely consumed. Except its potent pain relieving efficacy as reported, capsaicin also exerted its antitumor activity in several tumor models. Here, we reported that capsaicin had a profound anti-proliferative effect on human colon cancer cells via inducing cell cycle G0/G1 phase arrest and apoptosis, which was associated with an increase of p21, Bax and cleaved PARP. The underlying mechanism of capsaicin's antitumor potency was mainly attributed to the stabilization and activation of p53. Capsaicin substantially prolonged the half-life of p53 and significantly elevated the transcriptional activity of p53. Through suppressing the interaction between p53 and MDM2, MDM2-mediated p53 ubiquitination was remarkably decreased after capsaicin treatment, which resulted in the stabilization and accumulation of p53. The results of p53-shRNA experiment further demonstrated that p53 knockdown severely impaired the sensitivity of tested cells to capsaicin, G0/G1 phase arrest and the apoptosis induced by capsaicin in p53-knockdown cells was also dramatically decreased, implicating the important role of p53 played in capsaicin's antitumor activity. In summary, our data suggested that capsaicin, or a related analogue, may have a role in the management of human colon cancer.
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影响因子：
13.6
作者：
Dai C;Gu W
通讯作者：
Gu W
影响因子：
6.2
作者：
Mori, S;Ito, G;Sekido, Y
通讯作者：
Sekido, Y
影响因子：
2.8
作者：
Ip, S-W;Lan, S-H;Chung, J-G
通讯作者：
Chung, J-G
影响因子：
7.3
作者：
Elkablawy, MA;Maxwell, P;Hamilton, PW
通讯作者：
Hamilton, PW
DOI：
10.1155/2013/629750
发表时间：
2013
期刊：
Evidence-based complementary and alternative medicine : eCAM
影响因子：
--
作者：
Lin S;Zhang J;Chen H;Chen K;Lai F;Luo J;Wang Z;Bu H;Zhang R;Li H;Tong H
通讯作者：
Tong H