Pseudolaric acid B inhibits neuroglioma cell proliferation through DNA damage response

Song,Fengmei; Yu,Xiaoyan; Zhang,Haipeng; Wang,Zengyan; Wang,Yue; Meng,Xiangling; Yu,Jinghua

doi:10.3892/or.2017.5861

Pseudolaric acid B inhibits neuroglioma cell proliferation through DNA damage response

Authors:
- Fengmei Song
- Xiaoyan Yu
- Haipeng Zhang
- Zengyan Wang
- Yue Wang
- Xiangling Meng
- Jinghua Yu
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Affiliations: Institute of Virology and AIDS Research, The First Hospital of Jilin University, Jilin University, Changchun, Jilin 130021, P.R. China, Department of Experimental Pharmacology and Toxicology, School of Pharmacy, Jilin University, Changchun, Jilin 130000, P.R. China, Department of Gynaecology, 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, Chemistry of Traditional Chinese Medicine, College of Pharmacy, Changchun University of Chinese Medicine, Changchun, Jilin 130000, P.R. China
Published online on: August 1, 2017 https://doi.org/10.3892/or.2017.5861
Pages: 2211-2218

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Abstract

Human neuroglioma is one of the most common malignant intracranial tumors in neurosurgery, and accounts for more than 50% of all brain cancer cases. Thus, a clinically effective drug with which to treat neuroglioma is urgently required. Pseudolaric acid B (PAB), a diterpene acid isolated from the root and trunk bark of Pseudolarix kaempferi Gordon (Pinaceae), was found to inhibit cell growth in a variety of cancer cell lines, but to date the effect of PAB on neuroglioma remains unclear. MTT analysis confirmed that PAB inhibited neuroglioma A172 cell growth in a time- and dose-dependent manner. In addition, PAB influenced the aggregation of tubulin in A172 cells. Meanwhile following PAB treatment, a higher percentage of cells accumulated in the G2/M phase from 12 to 48 h, while at 36 h, cell cycle slippage into the G0/G1 phase, and at 48 h, slippage into the S phase was observed using flow cytometric analysis. Corresponding protein expression was consistent with the cell cycle alteration as detected by western blotting, and it was speculated that cell cycle slippage was related to reduced effectiveness of PAB which warrants further investigation. Meanwhile PAB induced cell death by regulating p38, ERK and JNK expression and activating the DNA damage response. Therefore, PAB plays an antitumor role in A172 cells, and may be a candidate drug for neuroglioma therapy.

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1	Gong X, Wang M, Tashiro S, Onodera S and Ikejima T: Involvement of JNK-initiated p53 accumulation and phosphorylation of p53 in pseudolaric acid B induced cell death. Exp Mol Med. 38:428–434. 2006. View Article : Google Scholar : PubMed/NCBI
2	Gong XF, Wang MW, Tashiro S, Onodera S and Ikejima T: Pseudolaric acid B induces apoptosis through p53 and Bax/Bcl-2 pathways in human melanoma A375-S2 cells. Arch Pharm Res. 28:68–72. 2005. View Article : Google Scholar : PubMed/NCBI
3	Pan DJ, Li ZL, Hu CQ, Chen K, Chang JJ and Lee KH: The cytotoxic principles of Pseudolarix kaempferi: Pseudolaric acid-A and -B and related derivatives. Planta Med. 56:383–385. 1990. View Article : Google Scholar : PubMed/NCBI
4	Yu J, Li X, Tashiro S, Onodera S and Ikejima T: Bcl-2 family proteins were involved in pseudolaric acid B-induced autophagy in murine fibrosarcoma L929 cells. J Pharmacol Sci. 107:295–302. 2008. View Article : Google Scholar : PubMed/NCBI
5	Yu JH, Cui Q, Jiang YY, Yang W, Tashiro S, Onodera S and Ikejima T: Pseudolaric acid B induces apoptosis, senescence, and mitotic arrest in human breast cancer MCF-7. Acta Pharmacol Sin. 28:1975–1983. 2007. View Article : Google Scholar : PubMed/NCBI
6	Yu JH, Wang HJ, Li XR, Tashiro S, Onodera S and Ikejima T: Protein tyrosine kinase, JNK, and ERK involvement in pseudolaric acid B-induced apoptosis of human breast cancer MCF-7 cells. Acta Pharmacol Sin. 29:1069–1076. 2008. View Article : Google Scholar : PubMed/NCBI
7	Shakur SF, Bit-Ivan E, Watkin WG, Merrell RT and Farhat HI: Multifocal and multicentric glioblastoma with leptomeningeal gliomatosis: A case report and review of the literature. Case Rep Med. 2013:1326792013. View Article : Google Scholar : PubMed/NCBI
8	Walker C, Baborie A, Crooks D, Wilkins S and Jenkinson MD: Biology, genetics and imaging of glial cell tumours. Br J Radiol. 84:S90–S106. 2011. View Article : Google Scholar : PubMed/NCBI
9	Parsons DW, Jones S, Zhang X, Lin JC, Leary RJ, Angenendt P, Mankoo P, Carter H, Siu IM, Gallia GL, et al: An integrated genomic analysis of human glioblastoma multiforme. Science. 321:1807–1812. 2008. View Article : Google Scholar : PubMed/NCBI
10	Lozano G and Elledge SJ: p53 sends nucleotides to repair DNA. Nature. 404:24–25. 2000. View Article : Google Scholar : PubMed/NCBI
11	Li FF, Yi S, Wen L, He J, Yang LJ, Zhao J, Zhang BP, Cui GH and Chen Y: Oridonin induces NPM mutant protein translocation and apoptosis in NPM1c+ acute myeloid leukemia cells in vitro. Acta Pharmacol Sin. 35:806–813. 2014. View Article : Google Scholar : PubMed/NCBI
12	Qi M, Yao G, Fan S, Cheng W, Tashiro S, Onodera S and Ikejima T: Pseudolaric acid B induces mitotic catastrophe followed by apoptotic cell death in murine fibrosarcoma L929 cells. Eur J Pharmacol. 683:16–26. 2012. View Article : Google Scholar : PubMed/NCBI
13	Klekotka PA, Santoro SA, Wang H and Zutter MM: Specific residues within the alpha 2 integrin subunit cytoplasmic domain regulate migration and cell cycle progression via distinct MAPK pathways. J Biol Chem. 276:32353–32361. 2001. View Article : Google Scholar : PubMed/NCBI
14	Xia Z, Dickens M, Raingeaud J, Davis RJ and Greenberg ME: Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science. 270:1326–1331. 1995. View Article : Google Scholar : PubMed/NCBI
15	Yoon S and Seger R: The extracellular signal-regulated kinase: Multiple substrates regulate diverse cellular functions. Growth Factors. 24:21–44. 2006. View Article : Google Scholar : PubMed/NCBI
16	Hartwell LH and Weinert TA: Checkpoints: Controls that ensure the order of cell cycle events. Science. 246:629–634. 1989. View Article : Google Scholar : PubMed/NCBI
17	Yu J, Ren P, Zhong T, Wang Y, Yan M, Xue B, Li R, Dai C, Liu C, Chen G, et al: Pseudolaric acid B inhibits proliferation in SW579 human thyroid squamous cell carcinoma. Mol Med Rep. 12:7195–7202. 2015. View Article : Google Scholar : PubMed/NCBI
18	Liu X, Chong Y, Tu Y, Liu N, Yue C, Qi Z, Liu H, Yao Y, Liu H, Gao S, et al: CRM1/XPO1 is associated with clinical outcome in glioma and represents a therapeutic target by perturbing multiple core pathways. J Hematol Oncol. 9:1082016. View Article : Google Scholar : PubMed/NCBI
19	Tong YG, Zhang XW, Geng MY, Yue JM, Xin XL, Tian F, Shen X, Tong LJ, Li MH, Zhang C, et al: Pseudolarix acid B, a new tubulin-binding agent, inhibits angiogenesis by interacting with a novel binding site on tubulin. Mol Pharmacol. 69:1226–1233. 2006. View Article : Google Scholar : PubMed/NCBI
20	Wong VK, Chiu P, Chung SS, Chow LM, Zhao YZ, Yang BB and Ko BC: Pseudolaric acid B, a novel microtubule-destabilizing agent that circumvents multidrug resistance phenotype and exhibits antitumor activity in vivo. Clin Cancer Res. 11:6002–6011. 2005. View Article : Google Scholar : PubMed/NCBI
21	Liu B, Dong H, Lin X, Yang X, Yue X, Yang J, Li Y, Wu L, Zhu X, Zhang S, et al: RND3 promotes Snail 1 protein degradation and inhibits glioblastoma cell migration and invasion. Oncotarget. 7:82411–82423. 2016.PubMed/NCBI