Activation of FOXO3 pathway is involved in polyphyllin I-induced apoptosis and cell cycle arrest in human bladder cancer cells

Jialin Li; Wenlong Ma; Xiangming Cheng; Xuebin Zhang; Yi Xie; Zhigang Ji; Song Wu

doi:10.1016/j.abb.2020.108363

Activation of FOXO3 pathway is involved in polyphyllin I-induced apoptosis and cell cycle arrest in human bladder cancer cells

Arch Biochem Biophys. 2020 Jul 15:687:108363. doi: 10.1016/j.abb.2020.108363. Epub 2020 Apr 23.

Authors

Jialin Li¹, Wenlong Ma², Xiangming Cheng³, Xuebin Zhang¹, Yi Xie¹, Zhigang Ji⁴, Song Wu⁵

Affiliations

¹ Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
² Urology Institute of Shenzhen University, The Third Affiliated Hospital of Shenzhen University, Shenzhen University, Shenzhen 518000, China; Shenzhen Following Precision Medical Research Institute, Luohu Hospital Group, Shenzhen 518000, China.
³ Department of Urology, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Jiangsu Provincial Hospital of Traditional Chinese Medicine, Nanjing 210000, China.
⁴ Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China. Electronic address: jizhigang@pumch.cn.
⁵ Urology Institute of Shenzhen University, The Third Affiliated Hospital of Shenzhen University, Shenzhen University, Shenzhen 518000, China; Shenzhen Following Precision Medical Research Institute, Luohu Hospital Group, Shenzhen 518000, China. Electronic address: wusong@szu.edu.cn.

PMID: 32335049
DOI: 10.1016/j.abb.2020.108363

Abstract

Polyphyllin I (PPI), an extract from Paris polyphylla, has been demonstrated to possess antitumor activity against multiple cancers. However, whether PPI can inhibit bladder cancer (BCa) and the underlying mechanisms have never been researched. In this study, we initially found that PPI could induce BCa cell apoptosis and cell cycle arrest, as well as inhibit cell proliferation in vitro. Additionally, PPI could effectively suppress the in vivo growth of BCa in the xenograft mice model. Furthermore, we found that forkhead box O3 (FOXO3) and its targets including BIM or NOXA were significantly upregulated in BCa cells following PPI treatment. Interestingly, we observed that FOXO3 knockdown partly reversed the effects of PPI on BCa cells. Taken together, our findings suggested that PPI exerted a cytotoxic effect in vitro and an antitumor activity in vivo against BCa partly by activating FOXO3 signaling pathway. Therefore, PPI may serve as a promising chemotherapy agent for BCa treatment.

Keywords: Apoptosis; Bladder cancer; Cell cycle arrest; FOXO3; Mitochondria; Polyphyllin I.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis / drug effects*
Cell Line, Tumor
Cell Proliferation / drug effects
Diosgenin / analogs & derivatives*
Diosgenin / therapeutic use
Female
Forkhead Box Protein O3 / genetics
Forkhead Box Protein O3 / metabolism*
G2 Phase Cell Cycle Checkpoints / drug effects
Gene Knockdown Techniques
Humans
Mice, Inbred BALB C
S Phase Cell Cycle Checkpoints / drug effects
Signal Transduction / drug effects*
Urinary Bladder Neoplasms / drug therapy*
Xenograft Model Antitumor Assays

Substances

FOXO3 protein, human
Forkhead Box Protein O3
polyphyllin I
Diosgenin