Jujuboside B Inhibits the Proliferation of Breast Cancer Cell Lines by Inducing Apoptosis and Autophagy

Lin Guo; Yupei Liang; Shiwen Wang; Lihui Li; Lili Cai; Yongqing Heng; Jing Yang; Xing Jin; Junqian Zhang; Shuying Yuan; Tong Xu; Lijun Jia

doi:10.3389/fphar.2021.668887

Jujuboside B Inhibits the Proliferation of Breast Cancer Cell Lines by Inducing Apoptosis and Autophagy

Front Pharmacol. 2021 Sep 24:12:668887. doi: 10.3389/fphar.2021.668887. eCollection 2021.

Authors

Lin Guo^{1

2}, Yupei Liang³, Shiwen Wang⁴, Lihui Li³, Lili Cai³, Yongqing Heng³, Jing Yang³, Xing Jin³, Junqian Zhang³, Shuying Yuan³, Tong Xu³, Lijun Jia^{1

3}

Affiliations

¹ Cancer Institute, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.
² Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
³ Cancer Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
⁴ Department of Laboratory Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, China.

Abstract

Jujuboside B (JB) is one of the main biologically active ingredients extracted from Zizyphi Spinosi Semen (ZSS), a widely used traditional Chinese medicine for treating insomnia and anxiety. Breast cancer is the most common cancer and the second leading cause of cancer-related death in women worldwide. The purpose of this study was to examine whether JB could prevent breast cancer and its underlying mechanism. First, we reported that JB induced apoptosis and autophagy in MDA-MB-231 and MCF-7 human breast cancer cell lines. Further mechanistic studies have revealed that JB-induced apoptosis was mediated by NOXA in both two cell lines. Moreover, the AMPK signaling pathway plays an important role in JB-induced autophagy in MCF-7. To confirm the anti-breast cancer effect of JB, the interaction of JB-induced apoptosis and autophagy was investigated by both pharmacological and genetic approaches. Results indicated that autophagy played a pro-survival role in attenuating apoptosis. Further in vivo study showed that JB significantly suppressed the growth of MDA-MB-231 and MCF-7 xenografts. In conclusion, our findings indicate that JB exerts its anti-breast cancer effect in association with the induction of apoptosis and autophagy.

Keywords: AMPK; NOXA; apoptosis; autophagy; breast cancer; jujuboside B.