Biomedical Science Letters (대한의생명과학회지)

The Korean Society for Biomedical Laboratory Sciences (대한의생명과학회)
권호 표지
DOI QR코드

DOI QR Code

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)
  • Received : 2019.09.23
  • Accepted : 2019.10.17
  • Published : 2019.12.31
Download PDF
⟨ Previous Next ⟩

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

References

  1. 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. https://doi.org/10.18632/oncotarget.16723
  2. 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.
  3. 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. https://doi.org/10.1093/abbs/gmu030
  4. 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. https://doi.org/10.1172/JCI67250
  5. Jozwiak-Bebenista M, Nowak JZ. Paracetamol: Mechanism of action, applications and safety concern. Acta Pol Pharm. 2014. 71: 11-23.
  6. 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.
  7. 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.
  8. 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. https://doi.org/10.2147/DDDT.S172199
  9. 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. https://doi.org/10.18632/oncotarget.4617
  10. 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:
  11. Petrich A, Nabhan C. Use of class i histone deacetylase inhibitor romidepsin in combination regimens. Leuk Lymphoma. 2016. 57: 1755-1765. https://doi.org/10.3109/10428194.2016.1160082
  12. 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. https://doi.org/10.18632/aging.100934
  13. Posadas I, Santos P, Cena V. Acetaminophen induces human neuroblastoma cell death through nfkb activation. PLoS One. 2012. 7: 16.
  14. 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. https://doi.org/10.3978/j.issn.2072-1439.2011.01.02
  15. 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. https://doi.org/10.4049/jimmunol.169.7.3536
  16. 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. https://doi.org/10.7150/jca.12286
  17. 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. https://doi.org/10.1158/0008-5472.CAN-17-1201
  18. 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.
  19. Slingerland M, Guchelaar HJ, Gelderblom H. Histone deacetylase inhibitors: An overview of the clinical studies in solid tumors. Anticancer Drugs. 2014. 25: 140-149. https://doi.org/10.1097/CAD.0000000000000040
  20. Stein JV, Nombela-Arrieta C. Chemokine control of lymphocyte trafficking: A general overview. Immunology. 2005. 116: 1-12. https://doi.org/10.1111/j.1365-2567.2005.02183.x
  21. Stennicke HR, Salvesen GS. Caspases - controlling intracellular signals by protease zymogen activation. Biochim Biophys Acta. 2000. 7: 1-2.
  22. 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.
  23. 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.
  24. 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. https://doi.org/10.1016/j.biopha.2007.06.002
  25. Ward SG, Westwick J. Chemokines: Understanding their role in t-lymphocyte biology. The Biochemical Journal. 1998. 333 (Pt 3): 457-470. https://doi.org/10.1042/bj3330457
  26. 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. https://doi.org/10.3892/mmr.2014.2085
  27. 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. https://doi.org/10.1158/1078-0432.CCR-15-2584