Knockdown of p62/sequestosome enhances ginsenoside Rh2-induced apoptosis in cervical cancer HeLa cells with no effect on autophagy

Shuai Bian; Yue Zhao; Fangyu Li; Shuyan Lu; Song Yang; Meichen Liu; Siming Wang; Daqing Zhao; Wei Zhang; Jiawen Wang

doi:10.1093/bbb/zbab019

Knockdown of p62/sequestosome enhances ginsenoside Rh2-induced apoptosis in cervical cancer HeLa cells with no effect on autophagy

Biosci Biotechnol Biochem. 2021 Apr 24;85(5):1097-1103. doi: 10.1093/bbb/zbab019.

Authors

Shuai Bian¹, Yue Zhao¹, Fangyu Li¹, Shuyan Lu¹, Song Yang¹, Meichen Liu¹, Siming Wang¹, Daqing Zhao¹, Wei Zhang², Jiawen Wang¹

Affiliations

¹ Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun, Jilin, China.
² Office of Academic Research, Changchun University of Chinese Medicine, Changchun, Jilin, China.

PMID: 33784737
DOI: 10.1093/bbb/zbab019

Abstract

p62/sequestosome is a multifunctional adaptor protein that participates in a wide variety of cellular processes. 20(S)-Ginsenoside Rh2 (G-Rh2) has various biological effects, including anticancer activity. We found that G-Rh2 can induce apoptosis and autophagy in HeLa cells. G-Rh2 significantly enhanced the transcriptional level of p62. A siRNA was constructed to knock down p62 and assess its effect on apoptosis induced by G-Rh2. p62 protein levels were successfully downregulated in cells transfected with the p62-specific siRNA. Silencing of p62 further decreased cell viability while also enhancing cell apoptosis, reactive oxygen species generation, the ratio of Bax to Bcl-2, and the cleavage of PARP. p62 knockdown decreased expression levels of Nrf2. Moreover, silencing of p62 had no significant effect on autophagy induced by G-Rh2. These results suggest that combining G-Rh2 treatment with inhibition of p62 may be a potential treatment strategy for cervical cancer.

Keywords: apoptosis; autophagy; ginsenoside G-Rh2; p62.

MeSH terms

Antineoplastic Agents, Phytogenic / pharmacology*
Apoptosis / drug effects*
Apoptosis / genetics
Autophagy
Autophagy-Related Protein 7 / genetics
Autophagy-Related Protein 7 / metabolism
Dose-Response Relationship, Drug
Gene Expression Regulation, Neoplastic / drug effects*
Ginsenosides / pharmacology*
HeLa Cells
Humans
Microtubule-Associated Proteins / genetics
Microtubule-Associated Proteins / metabolism
NF-E2-Related Factor 2 / genetics
NF-E2-Related Factor 2 / metabolism
Poly(ADP-ribose) Polymerases / genetics
Poly(ADP-ribose) Polymerases / metabolism
Proto-Oncogene Proteins c-bcl-2 / genetics
Proto-Oncogene Proteins c-bcl-2 / metabolism
RNA, Small Interfering / genetics
RNA, Small Interfering / metabolism
Reactive Oxygen Species / agonists
Reactive Oxygen Species / metabolism
Sequestosome-1 Protein / antagonists & inhibitors
Sequestosome-1 Protein / genetics*
Sequestosome-1 Protein / metabolism
Signal Transduction
bcl-2-Associated X Protein / genetics
bcl-2-Associated X Protein / metabolism

Substances

Antineoplastic Agents, Phytogenic
BAX protein, human
BCL2 protein, human
Ginsenosides
MAP1LC3B protein, human
Microtubule-Associated Proteins
NF-E2-Related Factor 2
NFE2L2 protein, human
Proto-Oncogene Proteins c-bcl-2
RNA, Small Interfering
Reactive Oxygen Species
SQSTM1 protein, human
Sequestosome-1 Protein
bcl-2-Associated X Protein
ginsenoside Rh2
Poly(ADP-ribose) Polymerases
ATG7 protein, human
Autophagy-Related Protein 7