J Cancer
2017; 8(13):2456-2470.
doi:10.7150/jca.19383 This issueCite
Research Paper
Sulforaphane Induced Apoptosis via Promotion of Mitochondrial Fusion and ERK1/2-Mediated 26S Proteasome Degradation of Novel Pro-survival Bim and Upregulation of Bax in Human Non-Small Cell Lung Cancer Cells
Yang Geng1, Yan Zhou1, Sai Wu1, Yabin Hu1, Kai Lin1, Yalin Wang1, Zhongnan Zheng1, Wei Wu1, 2✉
1. Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing, China; 2. Institute of Brain Tumor, Beijing Institute for Brain Disorders, Capital Medical University, Beijing, China.
✉ Corresponding author: Wei Wu, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, No. 10, Xitoutiao, You An Men Wai Ave, Feng Tai District Beijing 100069, China Tel: 011-8610-8391-1823 Fax: 011-8610-8391-1823 Email Address: weiwu207edu.cnMore
Citation:
Geng Y, Zhou Y, Wu S, Hu Y, Lin K, Wang Y, Zheng Z, Wu W. Sulforaphane Induced Apoptosis via Promotion of Mitochondrial Fusion and ERK1/2-Mediated 26S Proteasome Degradation of Novel Pro-survival Bim and Upregulation of Bax in Human Non-Small Cell Lung Cancer Cells. J Cancer 2017; 8(13):2456-2470. doi:10.7150/jca.19383. https://www.jcancer.org/v08p2456.htm
Previous studies in our laboratory showed that sulforaphane (SFN) induced apoptosis by sustained activation of extracellular regulated protein kinases 1/2 (ERK1/2). However, the underlying mechanisms associated with SFN-induced apoptosis and downstream cascades which are modulated by ERK1/2 were not elucidated. Herein we demonstrated for the first time that alteration of mitochondrial dynamics contributed to SFN-induced apoptosis in human non-small cell lung cancer (NSCLC) cells. Reports showed that protein Bim not only induced apoptosis but also promoted proliferation under certain circumstances. We found that Bim was related to cell growth in NSCLC cells. Pro-survival Bim downregulation was shown to induce apoptosis in response to SFN. Further, Using the ERK1/2 inhibitor, PD98059, we found that SFN upregulated Bax and downregulated Bim through the ERK1/2-dependent signaling pathway. Furthermore, SFN activated ERK1/2 to increase 26S proteasome activity to degrade Bim, while the proteasome inhibitor MG132 reversed this effect. Therefore, SFN phosphorylated ERK1/2 and activated the proteasome system leading to the degradation of Bim, which contributed to apoptosis in NSCLC cells. These findings provided a novel insight into SFN-related therapeutics in cancer treatment.
Geng, Y., Zhou, Y., Wu, S., Hu, Y., Lin, K., Wang, Y., Zheng, Z., Wu, W. (2017). Sulforaphane Induced Apoptosis via Promotion of Mitochondrial Fusion and ERK1/2-Mediated 26S Proteasome Degradation of Novel Pro-survival Bim and Upregulation of Bax in Human Non-Small Cell Lung Cancer Cells. Journal of Cancer, 8(13), 2456-2470. https://doi.org/10.7150/jca.19383.
ACS
Geng, Y.; Zhou, Y.; Wu, S.; Hu, Y.; Lin, K.; Wang, Y.; Zheng, Z.; Wu, W. Sulforaphane Induced Apoptosis via Promotion of Mitochondrial Fusion and ERK1/2-Mediated 26S Proteasome Degradation of Novel Pro-survival Bim and Upregulation of Bax in Human Non-Small Cell Lung Cancer Cells. J. Cancer 2017, 8 (13), 2456-2470. DOI: 10.7150/jca.19383.
NLM
Geng Y, Zhou Y, Wu S, Hu Y, Lin K, Wang Y, Zheng Z, Wu W. Sulforaphane Induced Apoptosis via Promotion of Mitochondrial Fusion and ERK1/2-Mediated 26S Proteasome Degradation of Novel Pro-survival Bim and Upregulation of Bax in Human Non-Small Cell Lung Cancer Cells. J Cancer 2017; 8(13):2456-2470. doi:10.7150/jca.19383. https://www.jcancer.org/v08p2456.htm
CSE
Geng Y, Zhou Y, Wu S, Hu Y, Lin K, Wang Y, Zheng Z, Wu W. 2017. Sulforaphane Induced Apoptosis via Promotion of Mitochondrial Fusion and ERK1/2-Mediated 26S Proteasome Degradation of Novel Pro-survival Bim and Upregulation of Bax in Human Non-Small Cell Lung Cancer Cells. J Cancer. 8(13):2456-2470.
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