PMID: 25742094Mar 6, 2015Paper

Ligustrazine Suppresses the Growth of HRPC Cells through the Inhibition of Cap- Dependent Translation Via Both the mTOR and the MEK/ERK Pathways

Anti-cancer Agents in Medicinal Chemistry
Jiaoyan HanXiang Xu

Abstract

Ligustrazine (TMP) has recently been used for the treatment of various cancers. However, its exact mechanisms of action, particularly the functions and the mechanisms of Ligustrazine in human hormone-refractory prostate cancer (HRPC), have not yet been extensively studied. Recently, our findings suggest that Ligustrazine dose- and time-dependently inhibits the growth of HRPC cells by reducing their proliferation and promoting apoptosis. Interestingly, the treatment of hormone-refractory prostate cancer (PC-3) cells with Ligustrazine results in a significant inhibition of the activation of mTOR and related downstream targets, which are critical for cell growth. Furthermore, pull-down assays with 7-methyl- GTP Sepharose 4B beads indicate that Ligustrazine reduces the available eIF4E for translation initiation. Accordingly, the results from the translation assay using a luciferase reporter system further demonstrate that Ligustrazine indeed inhibits cap-dependent translation. In addition, the transient overexpression of eIF4E or MNK1 prevents the Ligustrazine-induced inhibition of proliferation and confers significant protection against Ligustrazine-induced apoptosis. Therefore, the present study provides evidences that Ligustrazi...Continue Reading

Citations

Mar 11, 2017·Current Opinion in Oncology·Vidya P RamamurthyVincent C O Njar
Sep 4, 2015·ELife·Dale CowleyUNKNOWN Reproducibility Project Cancer Biology
Nov 6, 2018·International Journal of Molecular Medicine·Li LiKeji Chen
Nov 16, 2020·Genomics·Shi-Long JiangWen-Xu Hong
Jul 6, 2021·World Journal of Clinical Cases·Hua LiDeng-Xiang Liu

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