WASH regulates the oxidative stress Nrf2/ARE pathway to inhibit proliferation and promote apoptosis of HeLa cells under the action of Jolkinolide B

Author:

Hong Yu1,Liu Jicheng1,Kong Wanying1,Li Hui1,Cui Ying1,Liu Yuchao12,Deng Zhihui1,Ma Dezhi1,Zhang Keyong1,Li Jinghui1,Li Minhui123

Affiliation:

1. Qiqihaer Medical University, Qiqihaer, China

2. Baotou Medical College, Baotou, China

3. Inner Mongolia Hospital of Traditional Chinese Medicine, Hohhot, China

Abstract

Jolkinolide B (JB), a diterpenoid compound isolated from the roots of Euphorbia fischeriana, has gained research attention for its antitumor effects. In recent years, JB reportedly displayed anti-tumor activity in solid tumors, such as breast, ovarian, and prostate cancer, and leukemia. In this study, we evaluated the effect of JB on HeLa cells with a focus on cell growth inhibition and related mechanisms. HeLa cells were cultured in vitro and divided into a blank control group, HeLa-Scramble (0, 0.25, 0.5 mM), and Wiskott-Aldrich syndrome protein and SCAR homolog (WASH) protein silenced group, HeLa-shWASH (0, 0.25, 0.5 mM). Morphological changes were observed using an inverted microscope. The inhibition rate of cell proliferation was detected using the WST-1 method. Flow cytometry Brdu+PI double standard method was used to detect cell replication ability and FITC+PI double standard method was used to detect cell apoptosis rate. Western blot was used to verify the expression of Nrf2, HO-1, WASH, Bax, Bcl-2, and PCNA. The mRNA expression of cytokines (IL-1α, IL-6, and IL-8) was detected using RT-qPCR. The results showed that JB induced cell apoptosis and arrested cells at the G2/M phase in HeLa-shWASH cells compared with HeLa-Scramble cells (P < 0.05, P < 0.01, respectively). In addition, JB upregulated IL-1α, IL-6, and IL-8 in HeLa-shWASH cells. We conclude that WASH protein participates in JB-induced regulation of the Nrf2/ARE pathway, aggravates inflammatory responses, and promotes cancer cell apoptosis, thus inhibiting the proliferation and invasion abilities of HeLa cells. JB may have anti-tumor effects and potential clinical value for the treatment of cervical cancer.

Funder

Science and Technology Plan Joint Guidance Project, Qiqihar

Science and Technology Innovation Guidance Project, Inner Mongolia

Publisher

PeerJ

Subject

General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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