Berberine induces non-small cell lung cancer apoptosis via the activation of the ROS/ASK1/JNK pathway

Qianqian Chen; Yaqin Hou; Dan Li; Zhou Ding; Xiao Xu; Bingjie Hao; Qing Xia; Ming Li; Lihong Fan

doi:10.21037/atm-22-1298

Berberine induces non-small cell lung cancer apoptosis via the activation of the ROS/ASK1/JNK pathway

Ann Transl Med. 2022 Apr;10(8):485. doi: 10.21037/atm-22-1298.

Authors

Qianqian Chen^#¹, Yaqin Hou^#^{1

2}, Dan Li³, Zhou Ding¹, Xiao Xu², Bingjie Hao¹, Qing Xia¹, Ming Li¹, Lihong Fan^{1

2}

Affiliations

¹ Department of Respiratory and Critical Care Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
² Shanghai Clinical College, Anhui Medical University, Hefei, China.
³ Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.

^# Contributed equally.

Abstract

Background: Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers. Berberine (BBR), an isoquinoline alkaloid, is commonly used in traditional Chinese medicine. Previous studies have shown that BBR has a potential anti-tumor effect. However, the mechanisms of BBR on mitochondrial function in anti-lung cancer remain unknown. The aim of this study was to explore mitochondrial function in anti-tumor mechanisms of BBR in NSCLC.

Methods: The NSCLCs were cultured and treated with various doses (40, 80, 120 µg/mL) of BBR for 24 and 48 h. Cell viability was evaluated using Cell Counting Kit-8 (CCK-8). Cell apoptosis, reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were detected by flow cytometry. Relative protein expression was examined by western blot and immunohistochemical (IHC) analysis.

Results: BBR potently suppressed NSCLC cells growth by inducing apoptosis in a dose-and time-dependent manner. BBR induced apoptosis in NSCLC cells as evidenced by caspase-3 cleavage, cytochrome c release, and mitochondrial membrane depolarization. BBR-induced, dose-dependent induction of apoptosis was accompanied by sustained phosphorylation of c-jun-NH2-kinase (JNK) and the JNK inhibitor (SP600125) significantly suppressed BBR-induced apoptosis, N-acetyl cysteine (NAC), a ROS scavenger, was sufficient to both suppress apoptosis signal-regulating kinase 1 (ASK1) and JNK activation and disrupt apoptotic induction.

Conclusions: The results suggest that BBR induces apoptosis of NSCLC cells via ROS-mediated ASK1/JNK activation and the mitochondrial pathway.

Keywords: Berberine (BBR); apoptosis; mitochondria; non-small cell lung cancer (NSCLC); reactive oxygen species (ROS).