Picropodophyllin Inhibits the Proliferation of Human Prostate Cancer DU145 and LNCaP Cells via ROS Production and PI3K/AKT Pathway Inhibition

Xuejie Zhu; Xiaojie Chen; Guoli Wang; Dan Lei; Xiaoyu Chen; Kehao Lin; Minjing Li; Haiyan Lin; Defang Li; Qiusheng Zheng

doi:10.1248/bpb.b21-01006

Regular Articles

Picropodophyllin Inhibits the Proliferation of Human Prostate Cancer DU145 and LNCaP Cells via ROS Production and PI3K/AKT Pathway Inhibition

Xuejie Zhu, Xiaojie Chen, Guoli Wang, Dan Lei, Xiaoyu Chen, Kehao Lin, Minjing Li, Haiyan Lin, Defang Li , Qiusheng Zheng

Author information

Xuejie Zhu
Yantai Key Laboratory of Pharmacology of Traditional Chinese Medicine in Tumor Metabolism, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University
Collaborative Innovation Platform for Modernization and Industrialization of Regional Characteristic Traditional Chinese Medicine, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University
Xiaojie Chen
Yantai Key Laboratory of Pharmacology of Traditional Chinese Medicine in Tumor Metabolism, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University
Guoli Wang
Yantai Key Laboratory of Pharmacology of Traditional Chinese Medicine in Tumor Metabolism, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University
Dan Lei
Yantai Key Laboratory of Pharmacology of Traditional Chinese Medicine in Tumor Metabolism, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University
Xiaoyu Chen
Yantai Key Laboratory of Pharmacology of Traditional Chinese Medicine in Tumor Metabolism, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University
Kehao Lin
Yantai Key Laboratory of Pharmacology of Traditional Chinese Medicine in Tumor Metabolism, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University
Minjing Li
Yantai Key Laboratory of Pharmacology of Traditional Chinese Medicine in Tumor Metabolism, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University
Haiyan Lin
Yantai Key Laboratory of Pharmacology of Traditional Chinese Medicine in Tumor Metabolism, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University
Defang Li Corresponding author
Yantai Key Laboratory of Pharmacology of Traditional Chinese Medicine in Tumor Metabolism, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University
Collaborative Innovation Platform for Modernization and Industrialization of Regional Characteristic Traditional Chinese Medicine, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University
Qiusheng Zheng
Yantai Key Laboratory of Pharmacology of Traditional Chinese Medicine in Tumor Metabolism, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University
Key Laboratory of Xinjiang Endemic Phytomedicine Resources of Ministry of Education, School of Pharmacy, Shihezi University

Keywords: picropodophyllin, prostate cancer, proliferation, reactive oxygen species, phosphatidylinositol 3-kinase, protein kinase B signaling pathway

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2022 Volume 45 Issue 8 Pages 1027-1035

DOI https://doi.org/10.1248/bpb.b21-01006

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Abstract

The reactive oxygen species (ROS) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway play critical roles in the pathogenesis of prostate cancer by modulating cell proliferation. Picropodophyllin (PPP), an inhibitor of the insulin-like growth factor 1 receptor (IGF-1R), exerts significant antitumor effects via the PI3K/AKT signaling pathway. However, the effects of PPP on prostate cancer via ROS production and the PI3K/AKT signaling pathway remain elusive. Herein, we focused on examining the antitumor effects of PPP on DU145 and LNCaP human prostate cancer cells to determine the possible molecular mechanism. Our data indicated that the inhibitory effect of PPP on the proliferation of DU145 and LNCaP human prostate cancer cells was mediated by apoptosis induction and cell cycle blockade. Furthermore, PPP significantly influenced the expression of apoptosis-related, cell cycle, ROS production, and PI3K/AKT signaling proteins. These findings suggest that PPP can induce cell cycle arrest and apoptosis via the production of ROS and inhibition of PI3K/AKT signaling pathway, thereby suppressing the proliferation of prostate cancer cells.

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