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A375 melanoma cells are sensitized to cisplatin-induced toxicity by a synthetic nitro-flavone derivative 2-(4-Nitrophenyl)-4H-chromen-4-one through inhibition of PARP1

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Abstract

Background

Cisplatin has been extensively used in therapeutics for its broad-spectrum anticancer activity and frequently used for the treatment of solid tumors. However, it presents several side-effects and several cancers develop resistance. Combination therapy of cisplatin with poly (ADP-ribose) polymerase 1 (PARP1) inhibitors has been effective in increasing its efficacy at lower doses.

Methods and results

In this work, we have shown that the nitro-flavone derivative, 2-(4-Nitrophenyl)-4H-chromen-4-one (4NCO), can improve the sensitivity of cancer cells to cisplatin through inhibition of PARP1. The effect of 4NCO on cisplatin toxicity was studied through combination therapy in both exponential and density inhibited A375 melanoma cells. Combination index (CI) was determined from isobologram analysis. The mechanism of cell killing was assessed by lactate dehydrogenase (LDH) assay. Temporal nicotinamide adenine dinucleotide (NAD+) assay was done to show the inhibition of PARP1. We also performed in silico molecular modeling studies to know the binding mode of 4NCO to a modeled PARP1-DNA complex containing cisplatin-crosslinked adduct. The results from both in silico and in cellulo studies confirmed that PARP1 inhibition by 4NCO was most effective in sensitizing A375 melanoma cells to cisplatin. Isobologram analysis revealed that 4NCO reduced cell viability both in exponential and density inhibited A375 cells synergistically. The combination led to cell death through apoptosis.

Conclusion

The synthetic nitro-flavone derivative 4NCO effectively inhibited the important nuclear DNA repair enzyme PARP1 and therefore, could complement the DNA-damaging anticancer drug cisplatin in A375 cells and thus, could act as a potential adjuvant to cisplatin in melanoma therapy.

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Data availability

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References

  1. Dasari S, Bernard Tchounwou P (2014) Cisplatin in cancer therapy: Molecular mechanisms of action. Eur J Pharmacol. https://doi.org/10.1016/j.ejphar.2014.07.025

    Article  PubMed  PubMed Central  Google Scholar 

  2. Wang Z, Zhu G (2018) DNA Damage Repair Pathways and Repair of Cisplatin-Induced DNA Damage. Elsevier Inc, Amsterdam

    Book  Google Scholar 

  3. Shamsi MH, Kraatz HB (2013) Interactions of metal ions with DNA and some applications. J Inorg Organomet Polym Mater 23:4–23. https://doi.org/10.1007/s10904-012-9694-8

    Article  CAS  Google Scholar 

  4. Galluzzi L, Senovilla L, Vitale I, Michels J, Martins I, Kepp O, Castedo M, Kroemer G (2012) Molecular mechanisms of cisplatin resistance. Oncogene 31:1869–1883. https://doi.org/10.1038/onc.2011.384

    Article  CAS  PubMed  Google Scholar 

  5. Mezencev R (2015) Interactions of cisplatin with non-DNA targets and their influence on anticancer activity and drug toxicity: the complex world of the platinum complex. Curr Cancer Drug Targets 14:794–816. https://doi.org/10.2174/1568009614666141128105146

    Article  CAS  PubMed  Google Scholar 

  6. Makovec T (2019) Cisplatin and beyond: Molecular mechanisms of action and drug resistance development in cancer chemotherapy. Radiol Oncol 53:148–158. https://doi.org/10.2478/raon-2019-0018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Siddik ZH (2003) Cisplatin: Mode of cytotoxic action and molecular basis of resistance. Oncogene 22:7265–7279. https://doi.org/10.1038/sj.onc.1206933

    Article  CAS  PubMed  Google Scholar 

  8. Ma L, Wang H, Wang C, Su J, Xie Q, Xu L, Yu Y, Liu S, Li S, Xu Y, Li Z (2016) Failure of elevating calcium induces oxidative stress tolerance and imparts cisplatin resistance in ovarian cancer cells. Aging Dis 7:254–266. https://doi.org/10.14336/AD.2016.0118

    Article  PubMed  PubMed Central  Google Scholar 

  9. Shen DW, Pouliot LM, Hall MD, Gottesman MM (2012) Cisplatin resistance: A cellular self-defense mechanism resulting from multiple epigenetic and genetic changes. Pharmacol Rev 64:706–721. https://doi.org/10.1124/pr.111.005637

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Aldossary SA (2019) Review on pharmacology of cisplatin: Clinical use, toxicity and mechanism of resistance of cisplatin. Biomed Pharmacol J 12:7–15. https://doi.org/10.13005/bpj/1608

    Article  CAS  Google Scholar 

  11. Kubala M, Geleticova J, Huliciak M, Zatloukalova M, Vacek J, Sebela M (2014) Na+/K+-ATPase inhibition by cisplatin and consequences for cisplatin nephrotoxicity. Biomed Pap 158:194–200. https://doi.org/10.5507/bp.2014.018

    Article  Google Scholar 

  12. Howell SB, Safaei R, Larson CA, Sailor MJ (2010) Copper transporters and the cellular pharmacology of the platinum-containing cancer drugs. Mol Pharmacol 77:887–894. https://doi.org/10.1124/mol.109.063172.that

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Chen Z-S, Tiwari AK (2011) Multidrug resistance proteins (MRPs/ABCCs) in cancer chemotherapy and genetic diseases. FEBS J 278:3226–3245. https://doi.org/10.1111/j.1742-4658.2011.08235.x.Multidrug

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Michels J, Vitale I, Galluzzi L, Adam J, Olaussen KA, Kepp O, Senovilla L, Talhaoui I, Guegan J, Enot DP, Talbot M, Robin A, Girard P, Orear C, Lissa D, Sukkurwala AQ, Garcia P, Behnam-Motlagh P, Kohno K, Wu GS, Brenner C, Dessen P, Saparbaev M, Soria JC, Castedo M, Kroemer G (2013) Cisplatin resistance associated with PARP hyperactivation. Cancer Res 73:2271–2280. https://doi.org/10.1158/0008-5472.CAN-12-3000

    Article  CAS  PubMed  Google Scholar 

  15. Tanida S, Mizoshita T, Ozeki K, Tsukamoto H, Kamiya T, Kataoka H, Sakamuro D, Joh T (2012) Mechanisms of cisplatin-induced apoptosis and of cisplatin sensitivity: Potential of BIN1 to act as a potent predictor of cisplatin sensitivity in gastric cancer treatment. Int J Surg Oncol. https://doi.org/10.1155/2012/862879

    Article  PubMed  PubMed Central  Google Scholar 

  16. Basu A, Krishnamurthy S (2010) Cellular responses to cisplatin-induced DNA damage. J Nucleic Acids. https://doi.org/10.4061/2010/201367

    Article  PubMed  PubMed Central  Google Scholar 

  17. Karmakar S, Manna D, Ghosh S, Hansda S, Mitra A, Bagchi A, Ghosh R (2017) 9-Phenyl acridine: a possible poly ( ADP-ribose ) polymerase-1 inhibitor. J Chem Pharm Res 9:188–200

    CAS  Google Scholar 

  18. Karmakar S, Ghosh R (2018) Synergistic action of cisplatin and 9-phenyl acridine in A375 cells. Indian J Biochem Biophys 55:173–182

    CAS  Google Scholar 

  19. Geraets L, Moonen HJ, Brauers K, Wouters EF, Bast A, Hageman GJ (2007) Dietary flavones and flavonoles are inhibitors of poly(ADP-ribose)polymerase-1 in pulmonary epithelial cells. J Nutr 137:2190–2195. https://doi.org/10.1093/jn/137.10.2190

    Article  CAS  PubMed  Google Scholar 

  20. Mitra A, Biswas R, Bagchi A, Ghosh R (2019) Insight into the binding of a synthetic nitro-flavone derivative with human poly (ADP-ribose) polymerase 1. Int J Biol Macromol 141:444–459. https://doi.org/10.1016/j.ijbiomac.2019.08.242

    Article  CAS  PubMed  Google Scholar 

  21. Cushman M, Nagarathnam D, Burg DL, Geahlen RL (1991) Synthesis and protein-tyrosine kinase inhibitory activities of flavonoid analogues. J Med Chem 34:798–806. https://doi.org/10.1021/jm00106a047

    Article  CAS  PubMed  Google Scholar 

  22. Sekhar PN, Kishor PBK, Zubaidha PK, Hashmi AM, Kadam TA, Anandareddy L, De MM, Kumar KP, Bhaskar BV, Munichandrababu T, Jayasree G, Narayana PVBS, Gyananath G (2011) Experimental validation and docking studies of flavone derivatives on aldose reductase involved in diabetic retinopathy, neuropathy, and nephropathy. Med Chem Res 20:930–945. https://doi.org/10.1007/s00044-010-9412-4

    Article  CAS  Google Scholar 

  23. Nakanishi I, Murata K, Nagata N, Kurono M, Kinoshita T, Yasue M, Miyazaki T, Takei Y, Nakamura S, Sakurai A, Iwamoto N, Nishiwaki K, Nakaniwa T, Sekiguchi Y, Hirasawa A, Tsujimoto G, Kitaura K (2015) Identification of protein kinase CK2 inhibitors using solvent dipole ordering virtual screening. Eur J Med Chem 96:396–404. https://doi.org/10.1016/j.ejmech.2015.04.032

    Article  CAS  PubMed  Google Scholar 

  24. Wagal OS, Joshi AJ, Joshi UJ, Bhojwani HR, Begwani KV, Dawne HA, Gude RP, Sathaye SSKD (2021) Studies in molecular modeling, in-vitro CDK2 inhibition and antimetastatic activity of some synthetic flavones. Front Biosci (Landmark Ed) 26:664–681

    Article  Google Scholar 

  25. Mitra A, Saikh F, Das J, Ghosh S, Ghosh R (2018) Studies on the interaction of a synthetic nitro-flavone derivative with DNA: A multi-spectroscopic and molecular docking approach. Spectrochim Acta Part A Mol Biomol Spectrosc 203:357–369. https://doi.org/10.1016/j.saa.2018.05.073

    Article  CAS  Google Scholar 

  26. Masunaga S-I, Ono K, Abe M (1992) Potentially Lethal damage repair by quiescent cells in murine solid tumors. Int J Radiat Oncol 22:973–978

    Article  CAS  Google Scholar 

  27. Huang RY, Pei L, Liu Q, Chen S, Dou H, Shu G, Yuan ZX, Lin J, Peng G, Zhang W, Fu H (2019) Isobologram analysis: a comprehensive review of methodology and current research. Front Pharmacol 10:1–12. https://doi.org/10.3389/fphar.2019.01222

    Article  CAS  Google Scholar 

  28. Chou TC (2010) Drug combination studies and their synergy quantification using the chou-talalay method. Cancer Res 70:440–446. https://doi.org/10.1158/0008-5472.CAN-09-1947

    Article  CAS  PubMed  Google Scholar 

  29. Manna D, Bhuyan R, Saikh F, Ghosh S, Basak J, Ghosh R (2018) Novel 1,4-dihydropyridine induces apoptosis in human cancer cells through overexpression of Sirtuin1. Apoptosis 23:532–553. https://doi.org/10.1007/s10495-018-1483-6

    Article  CAS  PubMed  Google Scholar 

  30. Ghosh R, Guha D, Bhowmik S, Karmakar S (2013) Antioxidant enzymes and the mechanism of the bystander effect induced by ultraviolet C irradiation of A375 human melanoma cells. Mutat Res Genet Toxicol Environ Mutagen 757:83–90. https://doi.org/10.1016/j.mrgentox.2013.06.022

    Article  CAS  Google Scholar 

  31. Langelier M, Planck JL, Roy S, Pascal JM (2012) Structural basis for DNA damage-dependent poly(ADP-ribosyl)ation by human PARP-1. Science 336:728–732. https://doi.org/10.1126/science.1216338

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, I.N. Shindyalov PEB, (2000) The protein data bank. Nucleic Acids Res 28:235–242. https://doi.org/10.1093/nar/28.1.235

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Ramachandran GN, Ramakrishnan C, Sasisekharan V (1963) Stereochemistry of polypeptide chain configurations. J Mol Biol 7:95–99. https://doi.org/10.1016/S0022-2836(63)80023-6

    Article  CAS  PubMed  Google Scholar 

  34. Coste F, Malinge JM, Serre L, Shepard W, Roth M, Leng M, Zelwer C (1999) Crystal structure of a double-stranded DNA containing a cisplatin interstrand cross-link at 1.63 Å resolution: Hydration at the platinated site. Nucleic Acids Res 27:1837–1846. https://doi.org/10.1093/nar/27.8.1837

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Yan Y, Zhang D, Zhou P, Li B, Huang SY (2017) HDOCK: A web server for protein-protein and protein-DNA/RNA docking based on a hybrid strategy. Nucleic Acids Res 45:W365–W373. https://doi.org/10.1093/nar/gkx407

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Tuszynska I, Magnus M, Jonak K, Dawson W, Bujnicki JM (2015) NPDock: A web server for protein-nucleic acid docking. Nucleic Acids Res 43:W425–W430. https://doi.org/10.1093/nar/gkv493

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Schneidman-Duhovny D, Inbar Y, Nussinov R, Wolfson HJ (2005) PatchDock and SymmDock: Servers for rigid and symmetric docking. Nucleic Acids Res 33:363–367. https://doi.org/10.1093/nar/gki481

    Article  CAS  Google Scholar 

  38. (2018) ACD/Chemsketch version 2018.1 Advanced Chemistry Development, Inc., Toronto, ON, Canada, www.acdlabs.com

  39. The PyMOL Molecular Graphics System, Version 2.0 Schrödinger, LLC, DeLano WL (2002) Pymol An open-source Mol Graph tool. CCP4 Newsl Protein Crystallogr 40:82–92

    Google Scholar 

  40. Discovery Studio Visualizer Software, version 2.5. http://www.accelrys.com

  41. Macindoe G, Mavridis L, Venkatraman V, Devignes MD, Ritchie DW (2010) HexServer: An FFT-based protein docking server powered by graphics processors. Nucleic Acids Res 38:445–449. https://doi.org/10.1093/nar/gkq311

    Article  CAS  Google Scholar 

  42. Mann M, Kumar S, Sharma A, Chauhan SS, Bhatla N, Kumar S, Bakhshi S, Gupta R, Kumar L (2019) PARP inhibition enhances cisplatin sensitivity in cervical cancer by modulating β-catenin signaling. Ann Oncol 30:v19. https://doi.org/10.1093/annonc/mdz238.065

    Article  Google Scholar 

  43. Cheng H, Zhang Z, Borczuk A, Powell CA, Balajee AS, Lieberman HB, Halmos B (2013) PARP inhibition selectively increases sensitivity to cisplatin in ERCC1-low non-small cell lung cancer cells. Carcinogenesis 34:739–749. https://doi.org/10.1093/carcin/bgs393

    Article  CAS  PubMed  Google Scholar 

  44. Wang L, Liang C, Li F, Guan D, Wu X, Fu X, Lu A, Zhang G (2017) PARP1 in carcinomas and PARP1 inhibitors as antineoplastic drugs. Int J Mol Sci 18:1–16. https://doi.org/10.3390/ijms18102111

    Article  CAS  Google Scholar 

  45. Zheng YD, Xu XQ, Peng F, Yu JZ, Wu H (2011) The poly(ADP-ribose) polymerase-1 inhibitor 3-aminobenzamide suppresses cell growth and migration, enhancing suppressive effects of cisplatin in osteosarcoma cells. Oncol Rep 25:1399–1405. https://doi.org/10.3892/or.2011.1212

    Article  CAS  PubMed  Google Scholar 

  46. Swindall AF, Stanley JA, Yang ES (2013) PARP-1: Friend or foe of DNA damage and repair in tumorigenesis. Cancers (Basel) 5:943–958. https://doi.org/10.3390/cancers5030943

    Article  CAS  Google Scholar 

  47. Mitra A, Bhowmik S, Ghosh R (2021) Preferential interaction with c-MYC quadruplex DNA mediates the cytotoxic activity of a nitro-flavone derivative in A375 cells. J Photochem Photobiol 6:100033. https://doi.org/10.1016/j.jpap.2021.100033

    Article  Google Scholar 

  48. Song L, McNeil EM, Ritchie AM, Astell KR, Gourley C, Melton DW (2017) Melanoma cells replicate through chemotherapy by reducing levels of key homologous recombination protein RAD51 and increasing expression of translesion synthesis DNA polymerase ζ. BMC Cancer 17:1–14. https://doi.org/10.1186/s12885-017-3864-6

    Article  CAS  Google Scholar 

  49. Kauffmann A, Rosselli F, Lazar V, Winnepenninckx V, Mansuet-Lupo A, Dessen P, Van Den Oord JJ, Spatz A, Sarasin A (2008) High expression of DNA repair pathways is associated with metastasis in melanoma patients. Oncogene 27:565–573. https://doi.org/10.1038/sj.onc.1210700

    Article  CAS  PubMed  Google Scholar 

  50. Song L, Robson T, Doig T, Brenn T, Mathers M, Brown ER, Doherty V, Bartlett JMS, Anderson N, Melton DW (2013) DNA repair and replication proteins as prognostic markers in melanoma. Histopathology 62:343–350. https://doi.org/10.1111/j.1365-2559.2012.04362.x

    Article  PubMed  Google Scholar 

  51. Jewell R, Conway C, Mitra A, Randerson-Moor J, Lobo S, Nsengimana J, Harland M, Marples M, Edward S, Cook M, Powell B, Boon A, De Kort F, Parker KA, Cree IA, Barrett JH, Knowles MA, Bishop DT, Newton-Bishop J (2010) Patterns of expression of DNA repair genes and relapse from melanoma. Clin Cancer Res 16:5211–5221. https://doi.org/10.1158/1078-0432.CCR-10-1521

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Karwaciak I, Sałkowska A, Karaś K, Dastych J, Ratajewski M (2021) Targeting SIRT2 sensitizes melanoma cells to cisplatin via an EGFR-dependent mechanism. Int J Mol Sci 22:5034. https://doi.org/10.3390/ijms22095034

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Campagna R, Bacchetti T, Salvolini E, Pozzi V, Molinelli E, Brisigotti V, Sartini D, Campanati A, Ferretti G, Annamaria O, Emanuelli M (2020) Paraoxonase-2 silencing enhances sensitivity of A375 melanoma cells to treatment with cisplatin. Antioxidants 9:1238. https://doi.org/10.3390/antiox9121238

    Article  CAS  PubMed Central  Google Scholar 

  54. Quezada MJ, Picco ME, Villanueva MB, Castro MV, Barbero G, Fernández NB, Illescas E, Lopez-Bergami P (2021) BCL2L10 Is overexpressed in melanoma downstream of STAT3 and promotes cisplatin and ABT-737 resistance. Cancers (Basel) 13:78. https://doi.org/10.3390/cancers13010078

    Article  CAS  Google Scholar 

  55. Singleton KR, Crawford L, Tsui E, Manchester HE, Maertens O, Liu X, Liberti MV, Magpusao AN, Stein EM, Tingley JP, Frederick DT, Boland GM, Flaherty KT, McCall SJ, Krepler C, Sproesser K, Herlyn M, Adams DJ, Locasale JW, Cichowski K, Mukherjee S, Wood KC (2017) Melanoma therapeutic strategies that select against resistance by exploiting MYC-driven evolutionary convergence. Cell Rep 21:2796–2812. https://doi.org/10.1016/j.celrep.2017.11.022

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Malyuchenko NV, Kotova EY, Kulaeva OI, Kirpichnikov MP, Studitskiy VM (2015) PARP1 inhibitors: antitumor drug design. Acta Naturae 7:27–37

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Karam AK, Santiskulvong C, Fekete M, Zabih S, Eng C, Dorigo O (2010) Cisplatin and PI3kinase inhibition decrease invasion and migration of human ovarian carcinoma cells and regulate matrix-metalloproteinase expression. Cytoskeleton 67:535–544. https://doi.org/10.1002/cm.20465

    Article  CAS  PubMed  Google Scholar 

  58. Ghosh R, Bhattacharjee SB (1990) Killing and mutation induction in quiescent V79 cells as influenced by nalidixic acid. Mutat Res Lett 243:7–12. https://doi.org/10.1016/0165-7992(90)90116-2

    Article  CAS  Google Scholar 

  59. Florea AM, Büsselberg D (2011) Cisplatin as an anti-tumor drug: cellular mechanisms of activity, drug resistance and induced side effects. Cancers (Basel) 3:1351–1371. https://doi.org/10.3390/cancers3011351

    Article  CAS  Google Scholar 

  60. Ghosh (Datta) R, Bhattacharjee SB, (1989) Influence of benzamide on killing and mutation of density-inhibited V79 cells by MNNG. Mutat Res Lett 225:137–141. https://doi.org/10.1016/0165-7992(89)90131-0

    Article  Google Scholar 

  61. Curtin NJ (2008) PARP Inhibitors and Cancer Therapy. In: Curtin NJ (ed) Poly(ADP-Ribosyl)ation. Springer, Boston, pp 218–233

    Google Scholar 

  62. Kelley SK, Ashkenazi A (2004) Targeting death receptors in cancer with Apo2L/TRAIL. Curr Opin Pharmacol 4:333–339. https://doi.org/10.1016/j.coph.2004.02.006

    Article  CAS  PubMed  Google Scholar 

  63. Ghosh R, Girigoswami K, Guha D (2012) Suppression of apoptosis leads to cisplatin resistance in V79 cells subjected to chronic oxidative stress. Indian J Biochem Biophys 49:363–370

    CAS  PubMed  Google Scholar 

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Acknowledgements

The authors are grateful to Prof. S. Ghosh, Department of Chemistry, Jadavpur University for providing authentic samples of 4NCO for the work. The author, Anindita Mitra, acknowledges fellowship from Department of Science and Technology (DST-INSPIRE Grant: DST/INSPIRE Fellowship/2015/IF150061), Govt. of India. The authors also acknowledge the infrastructural facility at Department of Biotechnology (DBT) sponsored Bioinformatics Infrastructure Facility (BIF Centre), University of Kalyani for the work.

Funding

Department of Science & Technology—Promotion of University Research and Scientific Excellence II (DST-PURSE II), Govt. of India and University Grants Commission: Special Assistance Programme Departmental Research Support II (UGC-SAP DRS II), Govt. of India.

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Mitra, A., Ghosh, R. A375 melanoma cells are sensitized to cisplatin-induced toxicity by a synthetic nitro-flavone derivative 2-(4-Nitrophenyl)-4H-chromen-4-one through inhibition of PARP1. Mol Biol Rep 48, 5993–6005 (2021). https://doi.org/10.1007/s11033-021-06600-w

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