Bruceine D induces lung cancer cell apoptosis and autophagy via the ROS/MAPK signaling pathway in vitro and in vivo

Jiangjiang Fan,Huaran Zhang,Guotao Yang,Mingsheng Wu,Xiaoqing Liu,Dongmei Ren,Jinxia Wang

doi:10.1038/s41419-020-2317-3

Jiangjiang Fan, Huaran Zhang + Show 5 more

Open Access

https://doi.org/10.1038/s41419-020-2317-3

Copy DOI

Abstract

Worldwide, lung cancer remains a leading cause of cancer mortality. Bruceine D (BD) has been shown to induce pancreatic cancer cell death via several different mechanisms. In this study, we demonstrated that BD inhibited lung cancer cell proliferation. Apoptosis and autophagy were the most important mechanisms involved in BD-induced lung cancer cell death, and complete autophagic flux was observed in A549 and NCI-H292 cells. In addition, BD significantly improved intracellular reactive oxygen species (ROS) levels. BD-mediated cell apoptosis and autophagy were almost inhibited in cells pretreated with N-acetylcysteine (NAC), an ROS scavenger. Furthermore, MAPK signaling pathway activation contributed to BD-induced cell proliferation inhibition and NAC could eliminate p-ERK and p-JNK upregulation. Finally, an in vivo study indicated that BD inhibited the growth of lung cancer xenografts. Overall, BD is a promising candidate for the treatment of lung cancer owing to its multiple mechanisms and low toxicity.

Highlights

Lung cancer is the leading cause of cancer incidence death, with a 5-year survival rate of 18%1
Bruceine D (BD) inhibits the proliferation of A549 and NCI-H292 lung cancer cells in vitro A549 and NCI-H292 cells were exposed to different concentrations of BD for 24 h and 48 h
We found that BD, a quassinoid compound, has potential anticancer activity in A549 and NCI-H292 cells

Summary

Introduction

Lung cancer is the leading cause of cancer incidence death, with a 5-year survival rate of 18%1. Chemotherapeutic agents and therapeutic strategies have been developed for cancer treatment, the disease remains a critical challenge due to drug resistance, metastasis and low long-term survival rates[2,3]. The seeds of Brucea javanica have been used to treat inflammation, malaria, and warts for many years[4]. Growing evidence has indicated that Brucea javanica extracts exhibit potential anticancer activity[5,6,7]. BD, a quassinoid compound, can be extracted from the seeds of Brucea javanica. A previous study reported that BD induced PANC-1 apoptosis via activating the p38MAPK signaling pathway[8].

Methods

Results

Conclusion