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白藜芦醇诱导的细胞凋亡是由Hep G2细胞中p53依赖的途径介导的。

Resveratrol- induced apoptosis is mediated by p53-dependent pathway in Hep G2 cells.

作者信息

Kuo Po-Lin, Chiang Lien-Chai, Lin Chun-Ching

机构信息

Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung, 807, Taiwan.

出版信息

Life Sci. 2002 Nov 22;72(1):23-34. doi: 10.1016/s0024-3205(02)02177-x.

Abstract

Resveratrol, a phytoalexin found in many plants, has been reported to possess a wide range of pharmacological properties and is one of the promising chemopreventive agents for cancer. Here, we examined the antiproliferation effect of resveratrol in two human liver cancer cell lines, Hep G2 and Hep 3B. Our results showed that resveratrol inhibited cell growth in p53-positive Hep G2 cells only. This anticancer effect was a result of cellular apoptotic death induced by resveratrol via the p53-dependent pathway. Here we demonstrated that the resveratrol-treated cells were arrested in G1 phase and were associated with the increase of p21 expression. In addition, we also illustrated that the resveratrol-treated cells had enhanced Bax expression but they were not involved in Fas/APO-1 apoptotic signal pathway. In contrast, the p53-negative Hep 3B cells treated with resveratrol did not show the antiproliferation effect neither did they show significant changes in p21 nor Fas/APO-1 levels. In summary, our study demonstrated that the resveratrol effectively inhibited cell growth and induced programmed cell death in Hepatoma cells on a molecular basis. Furthermore, these results implied that resveratrol might also be a new potent chemopreventive drug candidate for liver cancer as it played an important role to trigger p53-mediated molecules involved in the mechanism of p53-dependent apoptotic signal pathway.

摘要

白藜芦醇是一种存在于许多植物中的植保素,据报道具有广泛的药理特性,是一种很有前景的癌症化学预防剂。在此,我们研究了白藜芦醇对两种人肝癌细胞系Hep G2和Hep 3B的抗增殖作用。我们的结果表明,白藜芦醇仅抑制p53阳性的Hep G2细胞的生长。这种抗癌作用是白藜芦醇通过p53依赖途径诱导细胞凋亡死亡的结果。在此我们证明,经白藜芦醇处理的细胞停滞在G1期,并与p21表达的增加有关。此外,我们还表明,经白藜芦醇处理的细胞中Bax表达增强,但它们不参与Fas/APO-1凋亡信号通路。相反,用白藜芦醇处理的p53阴性Hep 3B细胞既没有显示出抗增殖作用,p21和Fas/APO-1水平也没有显著变化。总之,我们的研究表明,白藜芦醇在分子水平上有效地抑制了肝癌细胞的生长并诱导了程序性细胞死亡。此外,这些结果表明,白藜芦醇可能也是一种新的有效的肝癌化学预防药物候选物,因为它在触发参与p53依赖凋亡信号通路机制的p53介导分子方面发挥了重要作用。

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