Browse > Article
http://dx.doi.org/10.15616/BSL.2019.25.4.293

Improving Combination Cancer Therapy by Acetaminophen and Romidepsin in Non-small Cell Lung Cancer Cells  

Lee, Seong-Min (Department of Biomedical Laboratory Science, Konyang University)
Park, James S. (Department of Medicine, NYU Langone Health)
Kim, Keun-Sik (Department of Biomedical Laboratory Science, Konyang University)
Publication Information
Biomedical Science Letters / v.25, no.4, 2019 , pp. 293-301 More about this Journal
Abstract
Combination chemotherapy is more effective than mono-chemotherapy and is widely used in clinical practice for enhanced cancer treatment. In this study, we investigated the potential synergistic effects of acetaminophen, a common component in many cold medicines, and romidepsin, a histone deacetylase (HDAC) inhibitor, in the A549 non-small cell lung cancer (NSCLC) cell line. The combination of acetaminophen and romidepsin also exerted significant cytotoxicity and apoptosis induced by activation of caspase-3 on tumor cells in vitro. Moreover, combination therapy significantly induced increased production of chemokines that stimulate migration of activated T-cells into tumor cells. This mechanism can lead to active T-cell mediated anti-tumor immunity in addition to the direct cytotoxic chemotherapeutic effect. Activated T-cells led to enhanced cytotoxicity in drug-treated A549 cells through interaction with tumor cells. These results suggested that the interaction between the two drugs is synergistic and significant. In conclusion, our data showed that the use of romidepsin and low concentrations acetaminophen could induce effective anti-tumor effects via enhanced tumor immune and direct cytotoxic chemotherapeutic responses. The combination of acetaminophen with romidepsin should be considered as a promising strategy for the treatment of lung cancer.
Keywords
Chemotherapy; Acetaminophen; Romidepsin; Histone deacetylase inhibitor; A549 cells;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Li Y, Hu T, Chen T, Yang T, Ren H, Chen M. Combination treatment of fty720 and cisplatin exhibits enhanced antitumour effects on cisplatin-resistant non-small lung cancer cells. Oncol Rep. 2018. 39: 565-572.
2 Liang YL, Zhang ZH, Liu XJ, Liu XQ, Tao L, Zhang YF, Wang H, Zhang C, Chen X, Xu DX. Melatonin protects against apoptosis-inducing factor (aif)-dependent cell death during acetaminophen-induced acute liver failure. PLoS One. 2012. 7: 18.
3 Liu J, Cheng H, Han L, Qiang Z, Zhang X, Gao W, Zhao K, Song Y. Synergistic combination therapy of lung cancer using paclitaxel- and triptolide-coloaded lipid-polymer hybrid nanoparticles. Drug Des Devel Ther. 2018. 12: 3199-3209.   DOI
4 Liu J, Li F, Ping Y, Wang L, Chen X, Wang D, Cao L, Zhao S, Li B, Kalinski P, Thorne SH, Zhang B, Zhang Y. Local production of the chemokines ccl5 and cxcl10 attracts cd8+ t lymphocytes into esophageal squamous cell carcinoma. Oncotarget. 2015. 6: 24978-24989.   DOI
5 Matsumoto R, Tsuda M, Yoshida K, Tanino M, Kimura T, Nishihara H, Abe T, Shinohara N, Nonomura K, Tanaka S. Aldo-keto reductase 1c1 induced by interleukin-1beta mediates the invasive potential and drug resistance of metastatic bladder cancer cells. Sci Rep. 2016. 6:
6 Petrich A, Nabhan C. Use of class i histone deacetylase inhibitor romidepsin in combination regimens. Leuk Lymphoma. 2016. 57: 1755-1765.   DOI
7 Pistritto G, Trisciuoglio D, Ceci C, Garufi A, D'Orazi G. Apoptosis as anticancer mechanism: Function and dysfunction of its modulators and targeted therapeutic strategies. Aging. 2016. 8: 603-619.   DOI
8 Posadas I, Santos P, Cena V. Acetaminophen induces human neuroblastoma cell death through nfkb activation. PLoS One. 2012. 7: 16.
9 Provencio M, Isla D, Sanchez A, Cantos B. Inoperable stage iii non-small cell lung cancer: Current treatment and role of vinorelbine. Journal of Thoracic Disease. 2011. 3: 197-204.   DOI
10 Qin Y, Camoretti-Mercado B, Blokh L, Long CG, Ko FD, Hamann KJ. Fas resistance of leukemic eosinophils is due to activation of nf-kappa b by fas ligation. J Immunol. 2002. 169: 3536-3544.   DOI
11 Slingerland M, Guchelaar HJ, Gelderblom H. Histone deacetylase inhibitors: An overview of the clinical studies in solid tumors. Anticancer Drugs. 2014. 25: 140-149.   DOI
12 Rivas-Fuentes S, Salgado-Aguayo A, Pertuz Belloso S, Gorocica Rosete P, Alvarado-Vasquez N, Aquino-Jarquin G. Role of chemokines in non-small cell lung cancer: Angiogenesis and inflammation. J Cancer. 2015. 6: 938-952.   DOI
13 Saputra EC, Huang L, Chen Y, Tucker-Kellogg L. Combination therapy and the evolution of resistance: The theoretical merits of synergism and antagonism in cancer. Cancer Res. 2018. 78: 2419-2431.   DOI
14 Sayour ME, Abd El Salam RM, Elyamany MF, El Sayed AM, El-Awady RA. Combination of paracetamol and the glutathione depleting agent buthionine sulfoximine show differential effect on liver cancer cells and normal hepatocytes. Pharmacology & Pharmacy. 2016. Vol.07 No.11: 17.
15 Stein JV, Nombela-Arrieta C. Chemokine control of lymphocyte trafficking: A general overview. Immunology. 2005. 116: 1-12.   DOI
16 Vinodhkumar R, Song YS, Devaki T. Romidepsin (depsipeptide) induced cell cycle arrest, apoptosis and histone hyperacetylation in lung carcinoma cells (A549) are associated with increase in p21 and hypophosphorylated retinoblastoma proteins expression. Biomed Pharmacother. 2008. 62: 85-93.   DOI
17 Stennicke HR, Salvesen GS. Caspases - controlling intracellular signals by protease zymogen activation. Biochim Biophys Acta. 2000. 7: 1-2.
18 Suraweera A, O'Byrne KJ, Richard DJ. Combination therapy with histone deacetylase inhibitors (hdaci) for the treatment of cancer: Achieving the full therapeutic potential of hdaci. Front Oncol. 2018. 8.
19 Valdez BC, Brammer JE, Li Y, Murray D, Liu Y, Hosing C, Nieto Y, Champlin RE, Andersson BS. Romidepsin targets multiple survival signaling pathways in malignant t cells. Blood Cancer J. 2015. 16: 83.
20 Ward SG, Westwick J. Chemokines: Understanding their role in t-lymphocyte biology. The Biochemical Journal. 1998. 333 (Pt 3): 457-470.   DOI
21 Yu YL, Yiang GT, Chou PL, Tseng HH, Wu TK, Hung YT, Lin PS, Lin SY, Liu HC, Chang WJ, Wei CW. Dual role of acetaminophen in promoting hepatoma cell apoptosis and kidney fibroblast proliferation. Mol Med Rep. 2014. 9: 2077-2084.   DOI
22 Zheng H, Zhao W, Yan C, Watson CC, Massengill M, Xie M, Massengill C, Noyes DR, Martinez GV, Afzal R, Chen Z, Ren X, Antonia SJ, Haura EB, Ruffell B, Beg AA. Hdac inhibitors enhance t-cell chemokine expression and augment response to pd-1 immunotherapy in lung adenocarcinoma. Clin Cancer Res. 2016. 22: 4119-4132.   DOI
23 Hopewell EL, Zhao W, Fulp WJ, Bronk CC, Lopez AS, Massengill M, Antonia S, Celis E, Haura EB, Enkemann SA, Chen D-T, Beg AA. Lung tumor nf-${\kappa}b$ signaling promotes t cell-mediated immune surveillance. The Journal of Clinical Investigation. 2013. 123: 2509-2522.   DOI
24 Bayat Mokhtari R, Homayouni TS, Baluch N, Morgatskaya E, Kumar S, Das B, Yeger H. Combination therapy in combating cancer. Oncotarget. 2017. 8: 38022-38043.   DOI
25 Bundscherer AC, Malsy M, Gruber MA, Graf BM, Sinner B. Acetaminophen and metamizole induce apoptosis in ht 29 and sw 480 colon carcinoma cell lines in vitro. Anticancer Res. 2018. 38: 745-751.
26 Gao M, Gao L, Tao Y, Hou J, Yang G, Wu X, Xu H, Tompkins VS, Han Y, Wu H, Zhan F, Shi J. Proteasome inhibitor carfilzomib interacts synergistically with histone deacetylase inhibitor vorinostat in jurkat t-leukemia cells. Acta Biochim Biophys Sin. 2014. 46: 484-491.   DOI
27 Jozwiak-Bebenista M, Nowak JZ. Paracetamol: Mechanism of action, applications and safety concern. Acta Pol Pharm. 2014. 71: 11-23.