Pseudolaric acid B induced autophagy, but not apoptosis, in MRC5 human fibroblast cells

Wang,Yue; Gao,Hongmei; Wu,Ting; Wang,Zengyan; Song,Fengmei; Chen,Antian; Zhang,Jing; Zhang,Wenyan; Zhang,Hui; Yu,Jinghua

doi:10.3892/ol.2017.7426

Pseudolaric acid B induced autophagy, but not apoptosis, in MRC5 human fibroblast cells

Authors:
- Yue Wang
- Hongmei Gao
- Ting Wu
- Zengyan Wang
- Fengmei Song
- Antian Chen
- Jing Zhang
- Wenyan Zhang
- Hui Zhang
- Jinghua Yu
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Affiliations: Research Institute of Virology and AIDS Research, The First Hospital of Jilin University, Jilin University, Changchun, Jilin 130021, P.R. China, Medicinal Chemistry, College of Pharmacy, Changchun University of Chinese Medicine, Changchun, Jilin 130021, P.R. China, Neonatal Intensive Care Unit, The First Hospital of Jilin University, Jilin University, Changchun, Jilin 130000, P.R. China, Department of Internal Medicine, The First Hospital of Jilin University, Jilin University, Changchun, Jilin 130000, P.R. China, Department of Experimental Pharmacology and Toxicology, School of Pharmacy, Jilin University, Changchun, Jilin 130000, P.R. China, College of Medicine, Norman Bethune Health Science Center, Jilin University, Changchun, Jilin 130000, P.R. China, Chemistry of Traditional Chinese Medicine, College of Pharmacy, Changchun University of Chinese Medicine, Changchun, Jilin 130000, P.R. China
Published online on: November 15, 2017 https://doi.org/10.3892/ol.2017.7426
Pages: 863-870
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Autophagy and apoptosis are closely associated. In previous studies, pseudolaric acid B (PAB), a diterpene acid isolated from the root and trunk bark of Pseudolarix kaempferi Gordon (Pinaceae), was demonstrated to induce apoptosis in various cell lines. However, in L929 murine fibrosarcoma and SW579 human thyroid squamous cell carcinoma cells, only autophagy was induced. In the present study, another cell line, MRC5 human lung fibroblast cells, was identified in which PAB only induced autophagy. The relationship between apoptosis and autophagy subsequent to PAB treatment in MRC5 cells was explored. When autophagy was inhibited by 3‑methyladenine (3MA), apoptosis was induced in the PAB‑treated MRC5 cells. To study the mechanism for the promotion of apoptosis by 3MA in the PAB‑treated cells, the expression of members from the apoptotic signal pathways was assessed. As Bcl‑2, Bcl‑2 associated X and pro‑caspase‑9 expression following PAB treatment was not affected by 3MA treatment, it was determined that apoptosis was induced independent of the mitochondrial pathway of apoptosis. As Fas and pro‑caspase‑8 expression following PAB treatment were not altered by 3MA, it was further determined that the death receptor pathway was not induced. However, the phosphorylation of c‑Jun‑N‑terminal kinase and the expression of pro‑caspase‑3 were upregulated, and the phosphorylation of extracellular signal‑regulated kinase downregulated, by the combination of PAB and 3MA treatment compared with PAB alone. It was also observed that 3MA did not affect the microtubule aggregation ability of PAB. Therefore, inhibiting autophagy in MRC5 cells did not affect the role of PAB in microtubule aggregation, while apoptosis was induced. This may present a strategy to enhance the anti‑tumor effects of PAB.

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