Effects of histone deacetylase inhibitors on ATP‑binding cassette transporters in lung cancer A549 and colorectal cancer HCT116 cells Corrigendum in /10.3892/ol.2023.14084

Wang,Hao; Chi,Chun‑Hua; Zhang,Ying; Shi,Bin; Jia,Ru; Wang,Ben‑Jun

doi:10.3892/ol.2019.10319

Effects of histone deacetylase inhibitors on ATP‑binding cassette transporters in lung cancer A549 and colorectal cancer HCT116 cells

Corrigendum in: /10.3892/ol.2023.14084

Authors:
- Hao Wang
- Chun‑Hua Chi
- Ying Zhang
- Bin Shi
- Ru Jia
- Ben‑Jun Wang
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Affiliations: Department of Clinical Laboratory, The First Affiliated Hospital of University of Science and Technology of China, Hefei, Anhui 230001, P.R. China, Department of Anorectal Surgery, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250014, P.R. China, Anorectal Department of Traditional Chinese Medicine, The First Affiliated Hospital of University of Science and Technology of China, Hefei, Anhui 230001, P.R. China, Department of Anorectal Surgery, The Second Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui 230001, P.R. China
Published online on: May 6, 2019 https://doi.org/10.3892/ol.2019.10319
Pages: 63-71

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Abstract

Histone deacetylase (HDAC) inhibitors and DNA alkylators are effective components used in combination chemotherapy. In the present study, the effects of HDAC inhibitors on the expression of ATP‑binding cassette (ABC) transporters were investigated. It was observed that HDAC inhibitors induced the expression of multidrug‑resistant ABC transporters differently in lung cancer A549 cells than in colorectal cancer HCT116 cells. In these two cell lines, the HDAC inhibitors suberoylanilide hydroxamic acid (SAHA) and trichostatin A (TSA) significantly increased ABCB1 expression at the mRNA and protein levels, whereas they had no evident effect on ABCG2 protein expression. SAHA and TSA decreased ABCG2 mRNA expression in A549 cells and had no evident effect on ABCG2 mRNA expression in HCT116 cells. Notably, SAHA and TSA increased the mRNA expression levels of ABCC5, ABCC6, ABCC10, ABCC11 and ABCC12, as well as the protein expression levels of ABCC2, ABCC10 and ABCC12. By contrast, these inhibitors decreased the mRNA expression levels of ABCC1, ABCC2, ABCC3 and ABCC4, as well as the expression of ABCC1 and ABCC3 proteins. Furthermore, SAHA and TSA were found to downregulate HDAC3 and HDAC4, but not HDAC1 and HDAC2. Taken together, the results suggested that HDAC inhibitors work synergistically with DNA alkylators, in part, due to the inhibitory effect of these inhibitors on ABCC1 expression, which translocates these alkylators from inside to outside of cancer cells. These results further suggested the possibility of antagonism when HDAC inhibitors are combined with anthracyclines and other ABCB1 drug ligands in chemotherapy.

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1	Mohammad IS, He W and Yin L: Understanding of human ATP binding cassette superfamily and novel multidrug resistance modulators to overcome MDR. Biomed Pharmacother. 100:335–348. 2018. View Article : Google Scholar : PubMed/NCBI
2	Wang L, Tan RZ, Zhang ZX, Yin R, Zhang YL, Cui WJ and He T: Association between Twist and multidrug resistance gene-associated proteins in Taxol^®-resistant MCF-7 cells and a 293 cell model of Twist overexpression. Oncol Lett. 15:1058–1066. 2018.PubMed/NCBI
3	Fukuda Y and Schuetz JD: ABC transporters and their role in nucleoside and nucleotide drug resistance. Biochem Pharmacol. 83:1073–1083. 2012. View Article : Google Scholar : PubMed/NCBI
4	Chen ZS and Tiwari AK: Multidrug resistance proteins (MRPs/ABCCs) in cancer chemotherapy and genetic diseases. FEBS J. 278:3226–3245. 2011. View Article : Google Scholar : PubMed/NCBI
5	Liu YR, Liang L, Zhao JM, Zhang Y, Zhang M, Zhong WL, Zhang Q, Wei JJ, Li M, Yuan J, et al: Twist1 confers multidrug resistance in colon cancer through upregulation of ATP-binding cassette transporters. Oncotarget. 8:52901–52912. 2017.PubMed/NCBI
6	Norouzi-Barough L, Sarookhani M, Salehi R, Sharifi M and Moghbelinejad S: CRISPR/Cas9, a new approach to successful knockdown of ABCB1/P-glycoprotein and reversal of chemosensitivity in human epithelial ovarian cancer cell line. Iran J Basic Med Sci. 21:181–187. 2018.PubMed/NCBI
7	Ceballos MP, Rigalli JP, Cere LI, Semeniuk M, Catania VA and Ruiz ML: ABC transporters: Regulation and association with multidrug resistance in hepatocellular carcinoma and colorectal carcinoma. Curr Med Chem. 2018.
8	Maia RC, Vasconcelos FC, Souza PS and Rumjanek VM: Towards comprehension of the ABCB1/P-glycoprotein role in chronic myeloid leukemia. Molecules. 23:2018. View Article : Google Scholar
9	Assaraf YG: Molecular basis of antifolate resistance. Cancer Metastasis Rev. 26:153–181. 2007. View Article : Google Scholar : PubMed/NCBI
10	Borst P, Evers R, Kool M and Wijnholds J: A family of drug transporters: The multidrug resistance-associated proteins. J Natl Cancer Inst. 92:1295–1302. 2000. View Article : Google Scholar : PubMed/NCBI
11	Dean M, Hamon Y and Chimini G: The human ATP-binding cassette (ABC) transporter superfamily. J Lipid Res. 42:1007–1017. 2001.PubMed/NCBI
12	Wang J, Yunyun Z, Wang L, Chen X and Zhu Z: ABCG2 confers promotion in gastric cancer through modulating downstream CRKL in vitro combining with biostatistics mining. Oncotarget. 8:5256–5267. 2017.PubMed/NCBI
13	Kaehler M, Ruemenapp J, Gonnermann D, Nagel I, Bruhn O, Haenisch S, Ammerpohl O, Wesch D, Cascorbi I and Bruckmueller H: MicroRNA-212/ABCG2-axis contributes to development of imatinib-resistance in leukemic cells. Oncotarget. 8:92018–92031. 2017. View Article : Google Scholar : PubMed/NCBI
14	Gottesman MM, Fojo T and Bates SE: Multidrug resistance in cancer: Role of ATP-dependent transporters. Nat Rev Cancer. 2:48–58. 2002. View Article : Google Scholar : PubMed/NCBI
15	Ling V: Multidrug resistance: Molecular mechanisms and clinical relevance. Cancer Chemother Pharmacol (40 Suppl). S3–S8. 1997. View Article : Google Scholar
16	Xu W, Liu H, Liu ZG, Wang HS, Zhang F, Wang H, Zhang J, Chen JJ, Huang HJ, Tan Y, et al: Histone deacetylase inhibitors upregulate Snail via Smad2/3 phosphorylation and stabilization of Snail to promote metastasis of hepatoma cells. Cancer Lett. 420:1–13. 2018. View Article : Google Scholar : PubMed/NCBI
17	Jiang GM, Wang HS, Zhang F, Zhang KS, Liu ZC, Fang R, Wang H, Cai SH and Du J: Histone deacetylase inhibitor induction of epithelial-mesenchymal transitions via up-regulation of Snail facilitates cancer progression. Biochim Biophys Acta. 1833:663–671. 2013. View Article : Google Scholar : PubMed/NCBI
18	Botrugno OA, Santoro F and Minucci S: Histone deacetylase inhibitors as a new weapon in the arsenal of differentiation therapies of cancer. Cancer Lett. 280:134–144. 2009. View Article : Google Scholar : PubMed/NCBI
19	Ni X, Li L and Pan G: HDAC inhibitor-induced drug resistance involving ATP-binding cassette transporters (Review). Oncol Lett. 9:515–521. 2015. View Article : Google Scholar : PubMed/NCBI
20	Di Costanzo A, Del Gaudio N, Conte L, Dell'Aversana C, Vermeulen M, de Thé H, Migliaccio A, Nebbioso A and Altucci L: The HDAC inhibitor SAHA regulates CBX2 stability via a SUMO-triggered ubiquitin-mediated pathway in leukemia. Oncogene. 37:2559–2572. 2018. View Article : Google Scholar : PubMed/NCBI
21	Stimson L and La Thangue NB: Biomarkers for predicting clinical responses to HDAC inhibitors. Cancer Lett. 280:177–183. 2009. View Article : Google Scholar : PubMed/NCBI
22	Wang H, Huang C, Zhao L, Zhang H, Yang JM, Luo P, Zhan BX, Pan Q, Li J and Wang BL: Histone deacetylase inhibitors regulate P-gp expression in colorectal cancer via transcriptional activation and mRNA stabilization. Oncotarget. 7:49848–49858. 2016.PubMed/NCBI
23	Zhao L, Bin S, He HL, Yang JM, Pu YC, Gao CH, Wang H and Wang BL: Sodium butyrate increases P-gp expression in lung cancer by upregulation of STAT3 and mRNA stabilization of ABCB1. Anticancer Drugs. 29:227–233. 2018.PubMed/NCBI
24	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
25	Sharom FJ: The P-glycoprotein multidrug transporter. Essays Biochem. 50:161–178. 2011. View Article : Google Scholar : PubMed/NCBI
26	Han Z and Shi L: Long non-coding RNA LUCAT1 modulates methotrexate resistance in osteosarcoma via miR-200c/ABCB1 axis. Biochem Biophys Res Commun. 495:947–953. 2018. View Article : Google Scholar : PubMed/NCBI
27	Robey RW, Zhan Z, Piekarz RL, Kayastha GL, Fojo T and Bates SE: Increased MDR1 expression in normal and malignant peripheral blood mononuclear cells obtained from patients receiving depsipeptide (FR901228, FK228, NSC630176). Clin Cancer Res. 12:1547–1555. 2006. View Article : Google Scholar : PubMed/NCBI
28	Tabe Y, Konopleva M, Contractor R, Munsell M, Schober WD, Jin L, Tsutsumi-Ishii Y, Nagaoka I, Igari J and Andreeff M: Up-regulation of MDR1 and induction of doxorubicin resistance by histone deacetylase inhibitor depsipeptide (FK228) and ATRA in acute promyelocytic leukemia cells. Blood. 107:1546–1554. 2006. View Article : Google Scholar : PubMed/NCBI
29	Hauswald S, Duque-Afonso J, Wagner MM, Schertl FM, Lübbert M, Peschel C, Keller U and Licht T: Histone deacetylase inhibitors induce a very broad, pleiotropic anticancer drug resistance phenotype in acute myeloid leukemia cells by modulation of multiple ABC transporter genes. Clin Cancer Res. 15:3705–3715. 2009. View Article : Google Scholar : PubMed/NCBI
30	To KK, Polgar O, Huff LM, Morisaki K and Bates SE: Histone modifications at the ABCG2 promoter following treatment with histone deacetylase inhibitor mirror those in multidrug-resistant cells. Mol Cancer Res. 6:151–164. 2008. View Article : Google Scholar : PubMed/NCBI
31	Valdez BC, Li Y, Murray D, Brammer JE, Liu Y, Hosing C, Nieto Y, Champlin RE and Andersson BS: Differential effects of histone deacetylase inhibitors on cellular drug transporters and their implications for using epigenetic modifiers in combination chemotherapy. Oncotarget. 7:63829–63838. 2016. View Article : Google Scholar : PubMed/NCBI
32	Ménez C, Mselli-Lakhal L, Foucaud-Vignault M, Balaguer P, Alvinerie M and Lespine A: Ivermectin induces P-glycoprotein expression and function through mRNA stabilization in murine hepatocyte cell line. Biochem Pharmacol. 83:269–278. 2012. View Article : Google Scholar : PubMed/NCBI
33	Kim SH, Kang HJ, Na H and Lee MO: Trichostatin A enhances acetylation as well as protein stability of ERalpha through induction of p300 protein. Breast Cancer Res. 12:R222010. View Article : Google Scholar : PubMed/NCBI
34	Barski A, Cuddapah S, Cui K, Roh TY, Schones DE, Wang Z, Wei G, Chepelev I and Zhao K: High-resolution profiling of histone methylations in the human genome. Cell. 129:823–837. 2007. View Article : Google Scholar : PubMed/NCBI
35	Koch CM, Andrews RM, Flicek P, Dillon SC, Karaöz U, Clelland GK, Wilcox S, Beare DM, Fowler JC, Couttet P, et al: The landscape of histone modifications across 1% of the human genome in five human cell lines. Genome Res. 17:691–707. 2007. View Article : Google Scholar : PubMed/NCBI
36	Rosenfeld JA, Wang Z, Schones DE, Zhao K, DeSalle R and Zhang MQ: Determination of enriched histone modifications in non-genic portions of the human genome. BMC Genomics. 10:1432009. View Article : Google Scholar : PubMed/NCBI
37	Witt O, Deubzer HE, Milde T and Oehme I: HDAC family: What are the cancer relevant targets? Cancer Lett. 277:8–21. 2009. View Article : Google Scholar : PubMed/NCBI
38	Lee HA, Song MJ, Seok YM, Kang SH, Kim SY and Kim I: Histone deacetylase 3 and 4 complex stimulates the transcriptional activity of the mineralocorticoid receptor. PLoS One. 10:e01368012015. View Article : Google Scholar : PubMed/NCBI
39	Vaute O, Nicolas E, Vandel L and Trouche D: Functional and physical interaction between the histone methyl transferase Suv39H1 and histone deacetylases. Nucleic Acids Res. 30:475–481. 2002. View Article : Google Scholar : PubMed/NCBI
40	Johnson ZL and Chen J: ATP binding enables substrate release from multidrug resistance protein 1. Cell. 172:81–89.e10. 2018. View Article : Google Scholar : PubMed/NCBI
41	Valdez BC, Nieto Y, Murray D, Li Y, Wang G, Champlin RE and Andersson BS: Epigenetic modifiers enhance the synergistic cytotoxicity of combined nucleoside analog-DNA alkylating agents in lymphoma cell lines. Exp Hematol. 40:800–810. 2012. View Article : Google Scholar : PubMed/NCBI
42	Nieto Y, Valdez BC, Thall PF, Ahmed S, Jones RB, Hosing C, Popat U, Shpall EJ, Qazilbash M, Gulbis A, et al: Vorinostat combined with high-dose gemcitabine, busulfan, and melphalan with autologous stem cell transplantation in patients with refractory lymphomas. Biol Blood Marrow Transplant. 21:1914–1920. 2015. View Article : Google Scholar : PubMed/NCBI
43	Köck K, Grube M, Jedlitschky G, Oevermann L, Siegmund W, Ritter CA and Kroemer HK: Expression of adenosine triphosphate-binding cassette (ABC) drug transporters in peripheral blood cells: Relevance for physiology and pharmacotherapy. Clin Pharmacokinet. 46:449–470. 2007. View Article : Google Scholar : PubMed/NCBI