Trichostatin A mediates apoptosis of MDA-MB-231 cells via JNK / MAPK signaling pathway

Zhang Haiyan, Sun Lihui, Pan Hongming, Li Lin, Lian Jie, Yu Jing, Lang Weiya

Chinese Journal of Clinical Anatomy ›› 2021, Vol. 39 ›› Issue (2) : 174-181.

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Chinese Journal of Clinical Anatomy ›› 2021, Vol. 39 ›› Issue (2) : 174-181. DOI: 10.13418/j.issn.1001-165x.2021.02.011

Trichostatin A mediates apoptosis of MDA-MB-231 cells via JNK / MAPK signaling pathway

  • Zhang Haiyan, Sun Lihui, Pan Hongming, Li Lin, Lian Jie, Yu Jing, Lang Weiya 
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Abstract

 Objective To explore the effect and mechanism of Trichostatin A (TSA) on the cell proliferation and apoptosis of breast cancer MDA-MB-23. Methods MTT, plate cloning experiments, flow cytometry were used to detect the effect of TSA on cell biological functions. qPCR and Western blot were applied to detect the effect of TSA on proliferation, apoptosis and MAPK signaling pathway. Mechanisms were detect by JNK pathway inhibitor in treatment. Results TSA inhibited the proliferation and apoptosis of breast cancer MDA-MB-231 cells in a dose-dependent manner; TSA could block the cell cycle of breast cancer MDA-MB-231 cells in G1 phase. TSA could upregulate the expression of protein and mRNA on P21, caspase-3, Bax and p-JNK, and down-regulate the expression of protein and mRNA of cyclin D1, Cdk4 and Bcl-2. The inhibition of JNK pathway inhibited the expression of p-JNK and the total apoptosis rate of MDA-MB-231 cells. The expression of Caspase-3, Bax and Bcl-2 decreased. Conclusions TSA can induce the apoptosis of MDA-MB-231 cells, the mechanism of which is to regulate the expression of apoptotic protein and induce apoptosis through phosphorylation of JNK in MAPK signaling pathway.

Key words

TSA /  Breast cancer /  Cell proliferation and apoptosis /  JNK signaling pathway

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Zhang Haiyan, Sun Lihui, Pan Hongming, Li Lin, Lian Jie, Yu Jing, Lang Weiya. Trichostatin A mediates apoptosis of MDA-MB-231 cells via JNK / MAPK signaling pathway[J]. Chinese Journal of Clinical Anatomy. 2021, 39(2): 174-181 https://doi.org/10.13418/j.issn.1001-165x.2021.02.011

References

[1]  Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2018, 68(6): 394-424. DOI:3322/caac.21492.
[2]  Desantis CE, Ma J, Goding Sauer A, et al. Breast cancer statistics, 2017, racial disparity in mortality by state[J]. CA Cancer J Clin, 2017, 67(6): 439-448. DOI: 10.3322/caac.21412.
[3] Chen CQ, Chen CS, Chen JJ, et al. Histone deacetylases inhibitor trichostatin A increases the expression of Dleu2/miR-15a/16-1 via HDAC3 in non-small cell lung cancer[J]. Mol Cell Biochem, 2013, 383(1-2): 137-148. DOI: 10.1007/s11010-013-1762-z.
[4] Wang XX, Xu J, Wang H, et al. Trichostatin A, a histone deacetylase inhibitor, reverses epithelial-mesenchymal transition in colorectal cancer SW480 and prostate cancer PC3 cells[J]. Biochem Biophys Res Commun, 2015, 456(1):320-326. DOI: 10.1016/j.bbrc.2014.11.079.
[5] Liu JB, Li Y. Trichostatin A and Tamoxifen inhibit breast cancer cell growth by miR-204 and ERα reducing AKT/mTOR pathway[J]. Biochem Biophys Res Commun, 2015, 467(2): 242-247. DOI: 10.1016/j.bbrc.2015.09.182.
[6]  Davis KG, Orangio GR. Basic Science, Epidemiology, and Screening for Anal Intraepithelial Neoplasia and Its Relationship to Anal Squamous Cell Cancer[J]. Clin Colon Rect Surg, 2018, 31(6): 368-378. DOI: 10.1055/s-0038-1668107.
[7] Yang F, Shan P, Zhao N, et al. Development of hydroxamate based histone deacetylase inhibitors containing 1,2,4-oxadiazolemoiety core with antitumor activities[J]. Bioorg Med Chem Lett, 2018, 10(19): 51-57. DOI:10.1016/j.bmcl.2018.11.027.
[8] Lin WC, Hsu FS, et al. Trichostatin A, a histone deacetylase inhibitor, induces synergistic cytotoxicity with chemotherapy via suppression of Raf/MEK/ERK pathway in urothelial carcinoma[J]. J Mol (Berl), 2018, 96 (12): 1307-1318. DOI: 10.1007/s00109-018-1697-7.
[9]  Cappellacci L, Perinelli DR, Maggi F, et al. Recent progress in histone deacetylase inhibitors as anticancer agents[J]. Curr Med Chem, 2018, 11(6): 10-17. DOI: 10.2174/0929867325666181016163110.
[10] Bose P, Dai Y, Grant S. Histone deacetylase inhibitor (HDACI) mechanisms of action: Emerging insights[J]. Pharmacol Ther, 2014, 143(3): 323-336. DOI:10.1016/j.pharmthera.2014.04.004.
[11] Cheng WW, Zhang DM. Design, synthesis and biological evaluation of novel HDAC inhibitors: sulphur-containing zinc binding groups[J]. J Chin Pharmaceutical Sci, 2019, 28(06): 408-421. DOI: 10.1016/j.ejmech.2020.112648.
[12]孟瑾,刘新利,车玲等. 组蛋白去乙酰化酶抑制剂TSA抑制结肠癌HT29细胞增殖作用的机制研究[J].消化肿瘤杂志(电子版), 2019, 11(02): 88-93. DOI: 10.3969/j.issn.1674-7402.2019.02.005.
[13] Martínez-León E, Amable G, Jácamo R, et al. Protein kinase D1 inhibition interferes with mitosis progression[J]. J Cell Physiol, 2019, 234(11): 20510-20519. DOI: 10.1002/jcp.28651.
[14] Hamzeloo-Moghadam M, Aghaei M, Abdolmoham Madi MH, et al. Anticancer activity of britannin through the downregulation of cyclin D1 and CDK4 in human breast cancer cells[J]. J Cancer Res Ther, 2019, 15(5): 1105-1108. DOI: 10.4103/jcrt.JCRT_517_17.
[15] Park HS, Hwang HJ, Kim GY, et al. Induction of apoptosis by fucoidan in human leukemia U937 cells through activation of p38MAPK and modulation of Bcl-2 family[J]. Mar Drugs, 2013, 11(7): 2347-2364. DOI: 10.3390/md11072347.
[16] Zhou XC, Jiang WB, Liu ZS, et a1. Virus in fection and death receptor-mediated apoptosis[J].Viruses, 2017, 9(11): 316-334. DOI: 10.3390/v9110316.
[17] Liu YT, Hsieh MJ, Lin JT, et al. Erianin induces cell apoptosis through ERK pathway in human nasopharyngeal carcinoma[J]. Biomed Pharmacother, 2019, 111(3): 262-269. DOI: 10.1016/j.biopha. 2018. 12. 081.
[18] Burotto M, Chiou VL, Lee J, et al.The MAPK pathway across different malignancies: A new perspective[J]. Cancer, 2015, 120(22): 3446-3456. DOI: 10.1002/cncr.28864.
[19] Xue B,Wu W,Huang K,et al. Stromal cell-derived factor-1 (SDF-1) enhances cells invasion by ανβ6 integrin-mediated signaling in ovarian cancer[J]. Mol Cell Biochem,2013, 380(1/2): 177-184. DOI: 10.1359/jbmr.2003.18.8.1404.
[20] Zhang H, Zhao X, Liu HB, et al. Trichostatin A inhibits proliferation of PC3 prostate cancer cells by disrupting the EGFR pathway[J]. Oncol Lett, 2019, 18(1): 687-693. DOI: 10.3892/ol.2019.10384.
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