Apoptosis induced by bruceine D in human non‑small‑cell lung cancer cells involves mitochondrial ROS‑mediated death signaling

Xie,Jian‑Hui; Lai,Zheng‑Quan; Zheng,Xing‑Han; Xian,Yan‑Fang; Li,Qian; Ip,Siu‑Po; Xie,You‑Liang; Chen,Jian‑Nan; Su,Zi‑Ren; Lin,Zhi‑Xiu; Yang,Xiao‑Bo

doi:10.3892/ijmm.2019.4363

Apoptosis induced by bruceine D in human non‑small‑cell lung cancer cells involves mitochondrial ROS‑mediated death signaling

Authors:
- Jian‑Hui Xie
- Zheng‑Quan Lai
- Xing‑Han Zheng
- Yan‑Fang Xian
- Qian Li
- Siu‑Po Ip
- You‑Liang Xie
- Jian‑Nan Chen
- Zi‑Ren Su
- Zhi‑Xiu Lin
- Xiao‑Bo Yang
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Affiliations: Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510120, P.R. China, Department of Pharmacy, Shenzhen University General Hospital, Shenzhen University, Shenzhen, Guangdong 518000, P.R. China, Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, P.R. China, School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, SAR 999077, P.R. China
Published online on: October 3, 2019 https://doi.org/10.3892/ijmm.2019.4363
Pages: 2015-2026
Copyright: © Xie et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Bruceine D is one of the active components of Brucea javanica (L.) Merr., which is widely used to treat cancer in China. The aim of the present study was to evaluate the potential effect of bruceine D against non‑small‑cell lung cancer (NSCLC) cells and delineate its underlying mechanisms. The results indicated that treatment with bruceine D markedly inhibited the proliferation of wild‑type NSCLC cells and epidermal growth factor receptor‑mutant cells in a dose‑ and time‑dependent manner, and significantly decreased the colony‑forming ability and migration of A549 cells. Hoechst 33342 staining and flow cytometric analysis demonstrated that treatment with bruceine D effectively induced apoptosis of A549 cells. In addition, the proapoptotic effect of bruceine D was found to be associated with G0‑G1 cell cycle arrest, accumulation of intracellular reactive oxygen species (ROS) and malondialdehyde, depletion of glutathione levels and disruption of mitochondrial membrane potential. Additionally, pretreatment with N‑acetylcysteine, a ROS scavenger, significantly attenuated the bruceine D‑induced inhibition in A549 cells. Western blotting demonstrated that treatment with bruceine D significantly suppressed the expression of the anti‑apoptotic proteins Bcl‑2, Bcl‑xL and X‑linked inhibitor of apoptosis, enhanced the expression levels of apoptotic proteins Bax and Bak, and inhibited the expression of pro‑caspase‑3 and pro‑caspase‑8. Based on these results, it may be suggested that inhibition of A549 NSCLC cell proliferation by bruceine D is associated with the modulation of ROS‑mitochondrial‑mediated death signaling. This novel insight may provide further evidence to verify the anticancer efficacy of B. javanica, and support a role for bruceine D in the anti‑NSCLC treatment.

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