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Apoptotic and antioxidant effects in HCT-116 colorectal carcinoma cells by a spiro-acridine compound, AMTAC-06

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Abstract

Background

Acridine compounds have been described as promising anticancer agents. Previous studies showed that (E)-1’-((4-chlorobenzylidene)amino)-5’-oxo-1’,5’-dihydro-10H-spiro[acridine-9,2’-pyrrole]-4’-carbonitrile (AMTAC-06), a spiro-acridine compound, has antitumor activity on Ehrlich tumor and low toxicity. Herein, we investigated its antitumor effect against human cells in vitro.

Methods

MTT assay was used to assess cytotoxicity of AMTAC-06 (3.125–200 µM) against tumor and non-tumor cells, and the half-maximal inhibitory concentration (IC50) and the selectivity index (SI) were calculated. The effects on the cell cycle (propidium iodide—PI—staining), apoptosis (Annexin V-FITC/PI double staining by flow cytometry), and production of reactive oxygen species, ROS (DCFH assay) were also evaluated. Statistical analysis was achieved using ANOVA followed by Tukey's post-test.

Results

AMTAC-06 showed higher cytotoxicity against colorectal carcinoma HCT-116 cells (IC50: 12.62 µM). The SI showed that AMTAC-06 was more selective for HCT-116 cells (HaCaT SI: 1.41; PBMC SI: 0.62) than doxorubicin (HaCaT SI: 0.10; PBMC SI: 0.01). AMTAC-06 (15 and 30 µM) induced an increase in the sub-G1 peak (p < 0.000001) and cell cycle arrest in S phase (p = 0.003547). Moreover, treatment with this compound (15 and 30 µM) resulted in increased early (p < 0.000001) and late apoptotic cells (p < 0.000001). In addition, there was a reduction on ROS production (p < 0.000001).

Conclusions

AMTAC-06 presents anticancer activity against HCT-116 cells by regulating the cell cycle, inducing apoptosis and an antioxidant action.

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Fig. 1
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Abbreviations

AMTAC-06:

(E)-1’-((4-chlorobenzylidene)amino)-5’-oxo-1’,5’-dihydro-10H-spiro[acridine-9, 2’-pyrrole]-4’-carbonitrile

CRC:

Colorectal cancer

DCF:

2',7'-Dichlorofluorescein

DOXO:

Doxorubicin

FITC:

Fluorescein isothiocyanate

HaCaT:

Human keratinocyte cell line

HCT-116:

Colorectal carcinoma cell line

H2DCFDA:

2',7'-Dichlorodihydrofluorescein diacetate

HeLa:

Cervical cancer cell line

HL-60:

Acute promyelocytic leukemia cell line

H2O2 :

Hydrogen peroxide

IC50 :

Half-maximal inhibitory concentration

L929:

Murine fibroblast cell line

MCF-7:

Breast cancer cell line

MDA-MB-231:

Breast cancer cell line

MTT:

(3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide

PBMCs:

Peripheral blood mononuclear cells

PBS:

Phosphate-buffered saline

PC-3:

Prostate cancer cell line

PI:

Propidium iodide

ROS:

Reactive oxygen species

SI:

Selectivity Index

SK-MEL-28:

Melanoma cancer cell line

References

  1. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646–74. https://doi.org/10.1016/j.cell.2011.02.013.

    Article  CAS  PubMed  Google Scholar 

  2. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424. https://doi.org/10.3322/caac.21492.

    Article  PubMed  Google Scholar 

  3. Chen J, Li D, Li W, Yin J, Zhang Y, Yuan Z, et al. Design, synthesis and anticancer evaluation of acridine hydroxamic acid derivatives as dual Topo and HDAC inhibitors. Bioorg Med Chem. 2018;26:3958–66. https://doi.org/10.1016/j.bmc.2018.06.016.

    Article  CAS  PubMed  Google Scholar 

  4. Workman P, Draetta GF, Schellens JHM, Bernards R. How much longer will we put up With $100,000 cancer drugs? Cell. 2017;168:579–83. https://doi.org/10.1016/j.cell.2017.01.034.

    Article  CAS  PubMed  Google Scholar 

  5. Smith S, Prewett S. Principles of chemotherapy and radiotherapy. Obstet Gynaecol Reprod Med. 2017;27:206–12. https://doi.org/10.1016/j.ogrm.2017.04.006.

    Article  Google Scholar 

  6. Vasan N, Baselga J, Hyman DM. A view on drug resistance in cancer. Nature. 2019;575:299–309. https://doi.org/10.1038/s41586-019-1730-1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Olivier T, Haslam A, Prasad V. Anticancer drugs approved by the US food and drug administration from 2009 to 2020 according to their mechanism of action. JAMA Netw Open. 2021;4: e2138793. https://doi.org/10.1001/jamanetworkopen.2021.38793.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Kumar R, Kaur M, Kumari M. Acridine: a versatile heterocyclic nucleus. Acta Pol Pharm. 2012;69:3–9 (PMID: 22574501).

    CAS  PubMed  Google Scholar 

  9. Schmidt A, Liu M (2015) Recent advances in the chemistry of acridines. In: Scriven EFV Ramsden CA (eds) Advances in heterocyclic chemistry, vol 115. Elsevier Ltd. p 287–353. https://doi.org/10.1016/bs.aihch.2015.04.004.

  10. Gensicka-Kowalewska M, Cholewiński G, Dzierzbicka K. Recent developments in the synthesis and biological activity of acridine/acridone analogues. RSC Adv. 2017;7:15776–804. https://doi.org/10.1039/c7ra01026e.

    Article  CAS  Google Scholar 

  11. Chen R, Huo L, Jaiswal Y, Huang J, Zhong Z, Zhong J, et al. Design, synthesis, antimicrobial, and anticancer activities of acridine thiosemicarbazides derivatives. Molecules. 2019;24:1–15. https://doi.org/10.3390/molecules24112065.

    Article  CAS  Google Scholar 

  12. Oyedele AS, Bogan DN, Okoro CO. Synthesis, biological evaluation and virtual screening of some acridone derivatives as potential anticancer agents. Bioorg Med Chem. 2020;28: 115426. https://doi.org/10.1016/j.bmc.2020.115426.

    Article  CAS  PubMed  Google Scholar 

  13. Almeida SMV, Lafayette EA, Silva WL, de Lima Serafim V, Menezes TM, Neves JL, et al. New spiro-acridines: DNA interaction, antiproliferative activity and inhibition of human DNA topoisomerases. Int J Biol Macromol. 2016;92:467–75. https://doi.org/10.1016/j.ijbiomac.2016.07.057.

    Article  CAS  PubMed  Google Scholar 

  14. Gouveia RG, Ribeiro AG, Segundo MÂSP, de Oliveira JF, de Lima M do CA, de Lima Souza TRC, et al. Synthesis, DNA and protein interactions and human topoisomerase inhibition of novel Spiroacridine derivatives. Bioorg Med Chem 2018;26:5911–21. https://doi.org/10.1016/j.bmc.2018.10.038.

  15. Silva DKF, Duarte SS, Lisboa TM, Ferreira RC, Lopes ALDO, Carvalho D, Sobral MV. Antitumor effect of a novel spiro-acridine compound is associated with up-regulation of Th1-type responses and antiangiogenic action. Molecules. 2020;25(1):1–9. https://doi.org/10.3390/molecules25010029.

    Article  CAS  Google Scholar 

  16. Duarte SS, Frade Silva DK, Honorato Lisboa TM, Galdino Gouveia R, Carlos Ferreira R, de Moura RO, et al. Anticancer effect of a spiro-acridine compound involves immunomodulatory and anti-angiogenic actions. Anticancer Res. 2020;40:5049–57. https://doi.org/10.21873/anticanres.14508.

    Article  CAS  PubMed  Google Scholar 

  17. Almeida FS, Sousa GLS, Rocha JC, Ribeiro FF, de Oliveira MR, de Lima Grisi TCS, et al. In vitro anti-Leishmania activity and molecular docking of spiro-acridine compounds as potential multitarget agents against Leishmania infantum. Bioorganic Med Chem Lett. 2021. https://doi.org/10.1016/j.bmcl.2021.128289.

    Article  Google Scholar 

  18. Brattain MG, Fine WD, Khaled FM, Thompson J, Brattain DE. Heterogeneity of malignant cells from a human colonic carcinoma. Cancer Res. 1981;41:1751–6. https://doi.org/10.1007/BF00048384.

    Article  CAS  PubMed  Google Scholar 

  19. Sanford KK, Earle WR, Likely GD. The growth in vitro of single isolated tissue cells. J Natl Cancer Inst. 1948;9:229–46. https://doi.org/10.1093/jnci/9.3.229.

    Article  CAS  PubMed  Google Scholar 

  20. Collins SJ, Gallo RC, Gallagher RE. Continuous growth and differentiation of human myeloid leukaemic cells in suspension culture. Nature. 1977;270:347–9. https://doi.org/10.1038/270347a0.

    Article  CAS  PubMed  Google Scholar 

  21. Papini S, Cecchetti D, Campani D, Fitzgerald W, Grivel JC, Chen S, Margolis L, Revoltella RP. Isolation and clonal analysis of human epidermal keratinocyte stem cells in long-term culture. Stem Cells Meet Rep. 2003;21:481–94. https://doi.org/10.1634/stemcells.21-4-481.

    Article  Google Scholar 

  22. Wilson VG. Growth and differentiation of HaCaT keratinocytes. Methods Mol Biol. 2014;1195:33–41. https://doi.org/10.1007/7651_2013_42.

    Article  PubMed  Google Scholar 

  23. Cailleau R, Young R, Olivé M, Reeves WJ. Breast tumor cell lines from pleural effusions. J Natl Cancer Inst. 1974;53:661–74. https://doi.org/10.1093/jnci/53.3.661.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Ohnuki Y, Marnell MM, Babcock MS, Lechner JF, Kaighn ME. Chromosomal analysis of human prostatic adenocarcinoma cell lines. Cancer Res. 1980;40:524–34.

    CAS  PubMed  Google Scholar 

  25. Scherer WF, Syverton JT, Gey GO. Studies on the propagation in vitro of poliomyelitis viruses: IV. Viral multiplication in a stable strain of human malignant epithelial cells (strain hela) derived from an epidermoid carcinoma of the cervix. J Exp Med. 1953;97:695–710. https://doi.org/10.1084/jem.97.5.695.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Carey TE, Takahashi T, Resnick LA, Oettgen HF, Old LJ. Cell surface antigens of human malignant melanoma: mixed hemadsorption assays for humoral immunity to cultured autologous melanoma cells. Proc Natl Acad Sci USA. 1976;73:3278–82. https://doi.org/10.1073/pnas.73.9.3278.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Soule HD, Vazquez J, Long A, Albert S, Brennan M. A human cell line from a pleural effusion derived from a breast carcinoma. J Natl Cancer Inst. 1973;51:1409–16. https://doi.org/10.1093/jnci/51.5.1409.

    Article  CAS  PubMed  Google Scholar 

  28. Lisboa T, Silva D, Duarte S, Ferreira R, Andrade C, Lopes AL, et al. Toxicity and antitumor activity of a thiophene-acridine hybrid. Molecules. 2019. https://doi.org/10.3390/molecules25010064.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983;65:55–63. https://doi.org/10.1016/0022-1759(83)90303-4.

    Article  CAS  PubMed  Google Scholar 

  30. Pilon A, Brás AR, Côrte-Real L, Avecilla F, Costa PJ, Preto A, et al. A new family of iron(II)-cyclopentadienyl compounds shows strong activity against colorectal and triple negative breast cancer cells. Molecules. 2020. https://doi.org/10.3390/molecules25071592.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Cossarizza A, Ferraresi R, Troiano L, Roat E, Gibellini L, Bertoncelli L, et al. Simultaneous analysis of reactive oxygen species and reduced glutathione content in living cells by polychromatic flow cytometry. Nat Protoc. 2009;4:1790–7. https://doi.org/10.1038/nprot.2009.189.

    Article  CAS  PubMed  Google Scholar 

  32. Ferreira RC, Batista TM, Duarte SS, Silva DKF, Lisboa TMH, Cavalcanti RFP, et al. A novel piperine analogue exerts in vivo antitumor effect by inducing oxidative, antiangiogenic and immunomodulatory actions. Biomed Pharmacother. 2020;128: 110247. https://doi.org/10.1016/j.biopha.2020.110247.

    Article  CAS  PubMed  Google Scholar 

  33. Darzynkiewicz Z, Bedner E, Smolewski P. Flow cytometry in analysis of cell cycle and apoptosis. Semin Hematol. 2001;38:179–93. https://doi.org/10.1016/S0037-1963(01)90051-4.

    Article  CAS  PubMed  Google Scholar 

  34. Tan BL, Norhaizan ME. Manilkara zapota (L.) P. Royen leaf water extract triggered apoptosis and activated caspase-dependent pathway in HT-29 human colorectal cancer cell line. Biomed Pharmacother. 2019;110:748–57. https://doi.org/10.1016/j.biopha.2018.12.027.

    Article  CAS  PubMed  Google Scholar 

  35. Saraste A, Pulkki K. Morphologic and biochemical hallmarks of apoptosis. Cardiovasc Res. 2000;45:528–37. https://doi.org/10.1016/S0008-6363(99)00384-3.

    Article  CAS  PubMed  Google Scholar 

  36. Majtnerová P, Roušar T. An overview of apoptosis assays detecting DNA fragmentation. Mol Biol Rep. 2018;45:1469–78. https://doi.org/10.1007/s11033-018-4258-9.

    Article  CAS  PubMed  Google Scholar 

  37. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209–49. https://doi.org/10.3322/caac.21660.

    Article  PubMed  Google Scholar 

  38. Fu W, Li X, Lu X, Zhang L, Li R, Zhang N, et al. A novel acridine derivative, LS-1-10 inhibits autophagic degradation and triggers apoptosis in colon cancer cells. Cell Death Dis. 2017;8: e3086. https://doi.org/10.1038/cddis.2017.498.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Wagner AD, Grothey A, Andre T, Dixon JG, Wolmark N, Haller DG, et al. Sex and adverse events of adjuvant chemotherapy in colon cancer: an analysis of 34 640 patients in the ACCENT database. J Natl Cancer Inst. 2021;113:400–7. https://doi.org/10.1093/jnci/djaa124.

    Article  CAS  PubMed  Google Scholar 

  40. Mangueira VM, Batista TM, Brito MT, de Sousa TKG, da Cruz RMD, de Abrantes RA, et al. A new acridine derivative induces cell cycle arrest and antiangiogenic effect on Ehrlich ascites carcinoma model. Biomed Pharmacother. 2017;90:253–61. https://doi.org/10.1016/j.biopha.2017.03.049.

    Article  CAS  PubMed  Google Scholar 

  41. Szymański P, Olszewska P, Mikiciuk-Olasik E, Różalski A, Maszewska A, Markiewicz Ł, et al. Novel tetrahydroacridine and cyclopentaquinoline derivatives with fluorobenzoic acid moiety induce cell cycle arrest and apoptosis in lung cancer cells by activation of DNA damage signaling. Tumor Biol. 2017. https://doi.org/10.1177/1010428317695011.

    Article  Google Scholar 

  42. Zhou Q, You C, Zheng C, Gu Y, Gu H, Zhang R, et al. 3-Nitroacridine derivatives arrest cell cycle at G0/G1 phase and induce apoptosis in human breast cancer cells may act as DNA-target anticancer agents. Life Sci. 2018;206:1–9. https://doi.org/10.1016/j.lfs.2018.05.010.

    Article  CAS  PubMed  Google Scholar 

  43. Borowa-Mazgaj B, Mróz A, Augustin E, Paluszkiewicz E, Mazerska Z. The overexpression of CPR and P450 3A4 in pancreatic cancer cells changes the metabolic profile and increases the cytotoxicity and pro-apoptotic activity of acridine antitumor agent, C-1748. Biochem Pharmacol. 2017;142:21–38. https://doi.org/10.1016/j.bcp.2017.06.124.

    Article  CAS  PubMed  Google Scholar 

  44. Almeida SMV, Ribeiro AG, de Lima Silva GC, Ferreira Alves JE, Beltrão EIC, de Oliveira JF, et al. DNA binding and Topoisomerase inhibition: How can these mechanisms be explored to design more specific anticancer agents? Biomed Pharmacother. 2017;96:1538–56. https://doi.org/10.1016/j.biopha.2017.11.054.

    Article  CAS  PubMed  Google Scholar 

  45. Haider MR, Ahmad K, Siddiqui N, Ali Z, Akhtar MJ, Fuloria N, et al. Novel 9-(2-(1-arylethylidene)hydrazinyl)acridine derivatives: target topoisomerase 1 and growth inhibition of HeLa cancer cells. Bioorg Chem. 2019;88: 102962. https://doi.org/10.1016/j.bioorg.2019.102962.

    Article  CAS  PubMed  Google Scholar 

  46. Park EJ, Kwon HK, Choi YM, Shin HJ, Choi S. Doxorubicin induces cytotoxicity through upregulation of pERK-dependent ATF3. PLoS ONE. 2012;7:2–11. https://doi.org/10.1371/journal.pone.0044990.

    Article  CAS  Google Scholar 

  47. Girek M, Kłosiński K, Grobelski B, Pizzimenti S, Cucci MA, Daga M, et al. Novel tetrahydroacridine derivatives with iodobenzoic moieties induce G0/G1 cell cycle arrest and apoptosis in A549 non-small lung cancer and HT-29 colorectal cancer cells. Mol Cell Biochem. 2019;460:123–50. https://doi.org/10.1007/s11010-019-03576-x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Zhang B, Dou Z, Xiong Z, Wang N, He S, Yan X, et al. Design, synthesis and biological research of novel N-phenylbenzamide-4-methylamine acridine derivatives as potential topoisomerase I/II and apoptosis-inducing agents. Bioorg Med Chem Lett. 2019;29: 126714. https://doi.org/10.1016/j.bmcl.2019.126714.

    Article  CAS  PubMed  Google Scholar 

  49. Moloney JN, Cotter TG. ROS signalling in the biology of cancer. Semin Cell Dev Biol. 2018;80:50–64. https://doi.org/10.1016/j.semcdb.2017.05.023.

    Article  CAS  PubMed  Google Scholar 

  50. Fukai T, Ushio-Fukai M. Cross-talk between NADPH oxidase and mitochondria: role in ROS signaling and angiogenesis. Cells. 2020. https://doi.org/10.3390/cells9081849.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Kalirajan R, Kulshrestha V, Sankar S, Jubie S. Docking studies, synthesis, characterization of some novel oxazine substituted 9-anilinoacridine derivatives and evaluation for their antioxidant and anticancer activities as topoisomerase II inhibitors. Eur J Med Chem. 2012;56:217–24. https://doi.org/10.1016/j.ejmech.2012.08.025.

    Article  CAS  PubMed  Google Scholar 

  52. Thyagarajan A, Sahu RP. Potential contributions of antioxidants to cancer therapy: immunomodulation and radiosensitization. Integr Cancer Ther. 2018;17:210–6. https://doi.org/10.1177/1534735416681639.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We are grateful to Tomer Abramov and “Pontual Traduções” (www.pontualtraducoes.com.br) for revising the text of this manuscript.

Funding

This study was funded by the Public Call n. 03 Produtividade em Pesquisa PROPESQ/PRPG/UFPB PIG13275-2020, the Brazilian agency CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Finance Code 001) and FAPESQPB (Fundação de Apoio à Pesquisa do Estado da Paraíba, Finance Code 013/2018).

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Authors and Affiliations

  1. Postgraduation Program in Bioactive Natural and Synthetic Products, Federal University of Paraíba, João Pessoa, Paraíba, Brazil

    Sâmia Sousa Duarte, Daiana Karla Frade Silva, Thaís Mangeon Honorato Lisboa, Rawny Galdino Gouveia, Camyla Caroliny Neves de Andrade, Valgrícia Matias de Sousa, Rafael Carlos Ferreira, Leônia Maria Batista & Marianna Vieira Sobral

  2. Drug Development and Synthesis Laboratory, Department of Pharmacy, State University of Paraíba, João Pessoa, Paraíba, Brazil

    Ricardo Olimpio de Moura & Joilly Nilce Santana Gomes

  3. Invertebrate Immunology and Pathology Laboratory, Department of Molecular Biology, Federal University of Paraíba, João Pessoa, Paraíba, Brazil

    Patricia Mirella da Silva

  4. Cardiovascular Pharmacology Laboratory, Postgraduation Program in Bioactive Natural and Synthetic Products, Federal University of Paraíba, João Pessoa, Paraíba, Brazil

    Fátima de Lourdes Assunção Araújo de Azevedo

  5. Immunology of Infectious Diseases Laboratory, Biotechnology Center, Federal University of Paraíba, João Pessoa, Paraíba, Brazil

    Tatjana S. L. Keesen

  6. Department of Pharmaceutical Sciences, Federal University of Paraíba, João Pessoa, Paraíba, Brazil

    Juan Carlos Ramos Gonçalves, Leônia Maria Batista & Marianna Vieira Sobral

  7. Laboratório de Oncofarmacologia (Oncofar), Instituto de Pesquisa em Fármacos e Medicamentos (IPeFarM). Cidade Universitária, Campus I, João Pessoa, Paraíba, 58051-900, Brazil

    Marianna Vieira Sobral

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Contributions

SSD and MVS conceived and designed the experiments, analyzed the data and wrote the paper. SSD, DKFS, TMHL, CCNA, VMS and RCF performed the experiments. RGG, ROM and JNSG synthesized and provided the spiro-acridine compound. PMS, FLAAA and TSLK support the flow cytometry analysis. JCRG and LMB revised the manuscript. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Marianna Vieira Sobral.

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Duarte, S.S., Silva, D.K.F., Lisboa, T.M.H. et al. Apoptotic and antioxidant effects in HCT-116 colorectal carcinoma cells by a spiro-acridine compound, AMTAC-06. Pharmacol. Rep 74, 545–554 (2022). https://doi.org/10.1007/s43440-022-00357-0

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