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TEOA, a triterpenoid from Actinidia eriantha, induces autophagy in SW620 cells via endoplasmic reticulum stress and ROS-dependent mitophagy

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Abstract

2α,3α,24-Thrihydroxyurs-12-en-28-oicacid (TEOA), a pentacyclic triterpenoid, isolated from the roots of Actinidia eriantha, exhibits significant cytotoxicity against SW620, BGC-823, HepG-2, A549 and PC-3 cancer cells. In this study, we investigated the underlying molecular mechanism of the anticancer activity of TEOA in SW620 cells. We demonstrated that TEOA induced apoptosis through cleavage of caspase-9 and PARP in SW620 cells. In addition, evidence of TEOA-mediated autophagy included the induction of autophagolysosomes and activation of autophagic markers LC-3B and p62. Further analysis illustrated that TEOA promoted the phosphorylation of PERK and elF2α, followed by up-regulation of the downstream protein CHOP, suggesting the involvement of PERK/eIF2α/CHOP pathway and ER stress in TEOA-induced autophagy in SW620 cells. Meanwhile, TEOA-mediated PINK1, Parkin, ubiquitin and p62 activation revealed that TEOA induced specific autophagy-mitophagy in SW620 cells. Additionally, an antioxidant NAC attenuated the TEOA-induced mitophagy, indicating that TEOA triggers mitophagy via a ROS-dependent pathway. Collectively, our findings revealed a novel cellular mechanism of TEOA in the colon cancer cell line SW620, thus providing a molecular basis for developing TEOA into an anti-tumor candidate.

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Acknowledgements

This work was supported by the National Science Foundation of China (Grant No. 81473182), the Jiangsu Provincial Natural Science Foundation of China (Grant No. BK20161269) and the Jiangsu Technology Support Program (Grant No. BE2014654).

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Authors and Affiliations

  1. Institute of Biomedical Engineering, College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou, China

    Dandan Zhang, Cuixia Gao, Ruyi Li, Lin Zhang & Jingkui Tian

  2. Zhejiang-Malaysia Joint Research Center for Traditional Medicine, Zhejiang University, Hangzhou, China

    Jingkui Tian

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  1. Dandan Zhang
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Correspondence to Jingkui Tian.

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Zhang, D., Gao, C., Li, R. et al. TEOA, a triterpenoid from Actinidia eriantha, induces autophagy in SW620 cells via endoplasmic reticulum stress and ROS-dependent mitophagy. Arch. Pharm. Res. 40, 579–591 (2017). https://doi.org/10.1007/s12272-017-0899-9

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