小白菊内酯通过抑制宫颈癌中的PI3K/Akt信号通路诱导细胞凋亡和自噬。

Parthenolide induces apoptosis and autophagy through the suppression of PI3K/Akt signaling pathway in cervical cancer.

作者信息

Jeyamohan Sridharan, Moorthy Rajesh Kannan, Kannan Mahesh Kumar, Arockiam Antony Joseph Velanganni

机构信息

Molecular Oncology Laboratory, Department of Biochemistry, School of Life Sciences, Bharathidasan University, Tiruchirappalli, Tamilnadu, 620 024, India.

出版信息

Biotechnol Lett. 2016 Aug;38(8):1251-60. doi: 10.1007/s10529-016-2102-7. Epub 2016 Apr 21.

DOI:10.1007/s10529-016-2102-7

PMID:27099069

Abstract

OBJECTIVE

To investigate the effect of parthenolide on apoptosis and autophagy and to study the role of the PI3K/Akt signaling pathway in cervical cancer.

RESULTS

Parthenolide inhibits HeLa cell viability in a dose dependent-manner and was confirmed by MTT assay. Parthenolide (6 µM) induces mitochondrial-mediated apoptosis and autophagy by activation of caspase-3, upregulation of Bax, Beclin-1, ATG5, ATG3 and down-regulation of Bcl-2 and mTOR. Parthenolide also inhibits PI3K and Akt expression through activation of PTEN expression. Moreover, parthenolide induces generation of reactive oxygen species that leads to the loss of mitochondrial membrane potential.

CONCLUSION

Parthenolide induces apoptosis and autophagy-mediated growth inhibition in HeLa cells by suppressing the PI3K/Akt signaling pathway and mitochondrial membrane depolarization and ROS generation. Parthenolide may be a potential therapeutic agent for the treatment of cervical cancer.

摘要

目的

探讨小白菊内酯对细胞凋亡和自噬的影响，并研究PI3K/Akt信号通路在宫颈癌中的作用。

结果

MTT法证实，小白菊内酯以剂量依赖性方式抑制HeLa细胞活力。小白菊内酯（6 μM）通过激活caspase-3、上调Bax、Beclin-1、ATG5、ATG3以及下调Bcl-2和mTOR诱导线粒体介导的凋亡和自噬。小白菊内酯还通过激活PTEN表达抑制PI3K和Akt表达。此外，小白菊内酯诱导活性氧生成，导致线粒体膜电位丧失。