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β-carboline alkaloid harmine induces DNA damage and triggers apoptosis by a mitochondrial pathway: study in silico, in vitro and in vivo

  • Authors:
    • Nádia S.R.S. Mota
    • Maicon R. Kviecinski
    • Karina B. Felipe
    • Valdelúcia M.A.S. Grinevicius
    • Tâmila Siminski
    • Gabriela M. Almeida
    • Rodrigo C. Zeferino
    • Claus T. Pich
    • Danilo W. Filho
    • Rozangela C. Pedrosa
  • View Affiliations / Copyright

    Affiliations: Department of Biochemistry, Federal University of Santa Catarina (UFSC), Florianópolis, SC 88040-900, Brazil, Postgraduate Program of Health Sciences (PPGCS), University of Southern Santa Catarina (UNISUL), Palhoça, SC 88137-270, Brazil, Department of Clinical Analysis, Federal University of Paraná (UFPR), Curitiba, PR 80060-000, Brazil, Center for Sciences, Technologies and Health of the Araranguá Campus, Federal University of Santa Catarina (UFSC), Araranguá, SC 88905-120, Brazil, Department of Ecology and Zoology, Federal University of Santa Catarina (UFSC), Florianópolis, SC 88040-900, Brazil
    Copyright: © Mota et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 1
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    Published online on: May 12, 2020
       https://doi.org/10.3892/ijfn.2020.1
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Abstract

Harmine, a tricyclic β-carboline alkaloid is an important metabolite present in Passiflora incarnata L. and Passiflora edulis f. flavicarpa Degener. Fruits of these plants are highly consumed in tropical countries and are popularly known as passion fruit, a natural product with potential antitumour activity. The cytotoxicity and selectivity effects were evaluated in vitro using tumour cell lines (MCF-7, HeLa) and normal mouse fibroblasts (McCoy cells). Molecular assays were performed using CT-DNA analysed by UV-Visible spectroscopy, fluorescence spectroscopy and circular dichroism, followed by in silico simulation (AutoDock Vina and GROMACS) and Comet assay. In vitro antitumour activity was assessed in Balb/c mice bearing Ehrlich ascitic tumour. Harmine presented cytotoxicity and selectivity to tumour cells. Spectrometry, molecular simulations and Comet assay suggested that harmine binds onto DNA nucleo base pairs by intercalation, consequently inducing DNA fragmentation. Furthermore, harmine decreased the PARP1-dependent DNA repair mechanism, causing cell cycle arrest in the G2/M phase through inhibition of pRb phosphorylation and reduced expression of CDK2, cyclin A and cyclin B1. Moreover, harmine decreased mitochondrial membrane potential and caused mitochondrial-related cellular Bax-dependent and p53-independent apoptosis in MCF-7 cells. This β-carboline alkaloid also decreased tumour growth, body weight, volume of ascitic fluid and volume of packed tumour cells, while increased the non-viable/viable tumour cells ratio, which consequently increased the lifespan of animals bearing tumours. Mechanistically, our findings indicate a putative antitumor effect of harmine, which associates DNA damage, DNA repair repression, cell cycle arrest and triggering apoptosis through mitochondrial pathway. The results suggest that harmine, present in the pulp and seed of the passion fruit, could be used in future as a promising coadjutant anticancer agent and we suggest to address this fruit as a functional food.
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1 

World Health Organization (WHO): Cancer. WHO, Geneva, 2018. https://www.who.int/cancer/en/. Accessed September 12, 2018.

2 

Ali R, Mirza Z, Ashraf GMD, Kamal MA, Ansari SA, Damanhouri GA, Abuzenadah AM, Chaudhary AG and Sheikh IA: New anticancer agents: Recent developments in tumor therapy. Anticancer Res. 32:2999–3005. 2012.PubMed/NCBI

3 

Patel K, Gadewar M, Tripathi R, Prasad SK and Patel DK: A review on medicinal importance, pharmacological activity and bioanalytical aspects of beta-carboline alkaloid ‘Harmine’. Asian Pac J Trop Biomed. 2:660–664. 2012.PubMed/NCBI View Article : Google Scholar

4 

Piechowska P, Zawirska-Wojtasiak R and Mildner-Szkudlarz S: Bioactive β-carbolines in food: a review. Nutrients. 11:1–10. 2019.PubMed/NCBI View Article : Google Scholar

5 

Tsuchiya H, Shimizu H and Iinuma M: Beta-carboline alkaloids in crude drugs. Chem Pharm Bull (Tokyo). 47:440–443. 1999.

6 

Li S, Teng L, Liu W, Cheng X, Jianga B, Wang Z and Wang CH: Pharmacokinetic study of harmane and its 10 metabolites in rat after intravenous and oral administration by UPLC-ESI-MS/MS. Pharm Biol. 54:1768–1781. 2016.PubMed/NCBI View Article : Google Scholar

7 

Pierson JT, Dietzgen RG, Shaw PN, Roberts-Thomson SJ, Monteith GR and Gidley MJ: Major Australian tropical fruits biodiversity: Bioactive compounds and their bioactivities. Mol Nutr Food Res. 56:357–387. 2012.PubMed/NCBI View Article : Google Scholar

8 

Lam SK and Ng TB: Passiflin, a novel dimeric antifungal protein from seeds of the passion fruit. Phytomedicine. 16:172–180. 2009.PubMed/NCBI View Article : Google Scholar

9 

Ingale AG and Hivrale AU: Pharmacological studies of Passiflora sp. and their bioactive compounds. Afr J Plant Sci. 4:417–426. 2010.

10 

Zhang P, Huang CR, Wang W, Zhang XK, Chen JJ, Wang JJ, Lin C and Jiang JW: Harmine hydrochloride triggers G2 phase arrest and apoptosis in MGC-803 cells and SMMC-7721 cells by upregulating p21, activating caspase-8/Bid, and downregulating ERK/Bad pathway. Phytother Res. 30:31–40. 2016.PubMed/NCBI View Article : Google Scholar

11 

Sobhani AM, Ebrahimi SA and Mahmoudian M: An in vitro evaluation of human DNA topoisomerase I inhibition by Peganum harmala L. seeds extract and its β-carboline alkaloids. J Pharm Pharm Sci. 5:19–23. 2002.PubMed/NCBI

12 

Liu J, Li Q, Liu Z, Lin L, Zhang X, Cao M and Jiang J: Harmine induces cell cycle arrest and mitochondrial pathway-mediated cellular apoptosis in SW620 cells via inhibition of the Akt and ERK signaling pathways. Oncol Rep. 35:3363–3370. 2016.PubMed/NCBI View Article : Google Scholar

13 

Hamsa TP and Kuttan G: Harmine activates intrinsic and extrinsic pathways of apoptosis in B16F-10 melanoma. Chin Med. 6(11)2011.PubMed/NCBI View Article : Google Scholar

14 

Mosmann T: Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J Immunol Methods. 65:55–63. 1983.PubMed/NCBI View Article : Google Scholar

15 

Koch A, Tamez P, Pezzuto J and Soejarto D: Evaluation of plants used for antimalarial treatment by the Maasai of Kenya. J Ethnopharmacol. 101:95–99. 2005.PubMed/NCBI View Article : Google Scholar

16 

McGahon AJ, Martin SJ, Bissonnette RP, Mahboubi A, Shi Y, Mogil RJ, Nishioka WK and Green DR: The end of the (cell) line: Methods for the study of apoptosis in vitro. Methods Cell Biol. 46:153–185. 1995.PubMed/NCBI View Article : Google Scholar

17 

O'Reilly CM, Fogarty KE, Drummond RM, Tuft RA and Walsh JV Jr: Quantitative analysis of spontaneous mitochondrial depolarizations. Biophys J. 85:3350–3357. 2003.PubMed/NCBI View Article : Google Scholar

18 

Navarro M, Cisneros-Fajardo EJ, Fernandez-Mestre M, Arrieche D and Marchan E: Synthesis, characterization, DNA binding study and biological activity against Leishmania mexicana of [Cu(dppz)2]BF4. J Inorg Biochem. 97:364–369. 2003.PubMed/NCBI View Article : Google Scholar

19 

Da Silveira VC, Benezra H, Luz JS, Georg RC, Oliveira CC and Ferreira AMDC: Binding of oxindole-Schiff base copper (II) complexes to DNA and its modulation by the ligand. J Inorg Biochem. 105:1692–1703. 2011.PubMed/NCBI View Article : Google Scholar

20 

Bertoldo JB, Razzera G, Vernal J, Brod FCA, Arisi ACM and Terenzi H: Structural stability of Staphylococcus xylosus lipase is modulated by Zn(2+) ions. Biochim Biophys Acta. 1814:1120–1126. 2011.PubMed/NCBI View Article : Google Scholar

21 

Malinina L, Soler-López M, Aymamí J and Subirana JÁ: Intercalation of an acridine-peptide drug in an AA/TT base step in the crystal structure of [d(CGCGAATTCGCG)](2) with six duplexes and seven Mg(2+) ions in the asymmetric unit. Biochemistry. 41:9341–9348. 2002.PubMed/NCBI View Article : Google Scholar

22 

Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC and Ferrin TE and Ferrin TE: UCSF Chimera - a visualization system for exploratory research and analysis. J Comput Chem. 25:1605–1612. 2004.PubMed/NCBI View Article : Google Scholar

23 

Hornak V, Abel R, Okur A, Strockbine B, Roitberg A and Simmerling C: Comparison of multiple AMBER force fields and development of improved protein backbone parameters. Proteins. 65:712–725. 2006.PubMed/NCBI View Article : Google Scholar

24 

Sousa da Silva AW and Vranken WF: ACPYPE - AnteChamber PYthon Parser interfacE. BMC Res Notes. 5(367)2012.PubMed/NCBI View Article : Google Scholar

25 

Wang J, Wang W, Kollman PA and Case DA: Automatic atom type and bond type perception in molecular mechanical calculations. J Mol Graph Model. 25:247–260. 2006.PubMed/NCBI View Article : Google Scholar

26 

Forli S, Huey R, Pique ME, Sanner MF, Goodsell DS and Olson AJ and Olson AJ: Computational protein-ligand docking and virtual drug screening with the AutoDock suite. Nat Protoc. 11:905–919. 2016.PubMed/NCBI View Article : Google Scholar

27 

Trott O and Olson AJ: AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem. 31:455–461. 2010.PubMed/NCBI View Article : Google Scholar

28 

Schrödinger LCC: The PyMOL Molecular Graphics System, Version 1.8. Schrödinger. LCC, New York, NY, 2015.

29 

Laskowski RA and Swindells MB: LigPlot+: Multiple ligand-protein interaction diagrams for drug discovery. J Chem Inf Model. 51:2778–2786. 2011.PubMed/NCBI View Article : Google Scholar

30 

Hanwell MD, Curtis DE, Lonie DC, Vandermeersch T, Zurek E and Hutchison GR: Avogadro: An advanced semantic chemical editor, visualization, and analysis platform. J Cheminform. 4(17)2012.PubMed/NCBI View Article : Google Scholar

31 

Van Der Spoel D, Lindahl E, Hess B, Groenhof G, Mark AE and Berendsen HJC: GROMACS: Fast, Flexible, and Free. J Comput Chem. 26:1701–1718. 2005.PubMed/NCBI View Article : Google Scholar

32 

Abraham M, Hess B, Van Der Spoel D, Lindahl E and the GROMACS development team: GROMACS User Manual version 4, 2018. uriwww.gromacs.orghttps://www.gromacs.org.

33 

Jorgensen WL, Chandrasekhar J, Madura JD, Impey RW and Klein ML: Comparison of simple potential functions for simulating liquid water. J Chem Phys. 79:926–935. 1983.

34 

Kumari R, Kumar R and Lynn A: Open Source Drug Discovery Consortium: g_mmpbsa - a GROMACS tool for high-throughput MM-PBSA calculations. J Chem Inf Model. 54:1951–1962. 2014.PubMed/NCBI View Article : Google Scholar

35 

Hsin J, Arkhipov A, Yin Y, Stone JE and Schulten K: Using VMD: an introductory tutorial. Curr Protoc Bioinformatics: CHAPTER: Unit–5.7, 2008.

36 

Verlet L: Computer ‘Experiments’ on Classical Fluids. I. Thermodynamical Properties of Lennard-Jones Molecules. Phys Rev. 159:98–103. 1967.

37 

Lemkul JA, Allen WJ and Bevan DR: Practical considerations for building GROMOS-compatible small-molecule topologies. J Chem Inf Model. 50:2221–2235. 2010.PubMed/NCBI View Article : Google Scholar

38 

Singh NP, McCoy MT, Tice RR and Schneider EL: A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res. 175:184–191. 1988.PubMed/NCBI View Article : Google Scholar

39 

Ross GM, McMillan TJ, Wilcox P and Collins AR: The single cell microgel electrophoresis assay (comet assay): Technical aspects and applications. Report on the 5th LH Gray Trust Workshop, Institute of Cancer Research, 1994. Mutat Res. 337:57–60. 1995.PubMed/NCBI View Article : Google Scholar

40 

Laemmli UK: Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 227:680–685. 1970.PubMed/NCBI View Article : Google Scholar

41 

Kviecinski MR, Benelli P, Felipe KB, Correia JFG, Pich CT, Ferreira SRS and Pedrosa RC: SFE from Bidens pilosa Linné to obtain extracts rich in cytotoxic polyacetilenes with antitumor activity. J Supercrit Fluids. 56:243–248. 2011.

42 

Hossain MA, Kim D, Jang JY, Kang YJ, Yoon JH, Moon JK, Chung HY, Kim GY, Choi YH, Copple BL and Kim ND: Aspirin enhances doxorubicin-induced apoptosis and reduces tumor growth in human hepatocellular carcinoma cells in vitro and in vivo. Int J Oncol. 40:1636–1642. 2012.PubMed/NCBI View Article : Google Scholar

43 

Felipe KB, Kviecinski MR, Ourique F, Bücker NF, Farias MS, Castro LSEPW, Grinevicius VMAS, Motta NS, Correia JFG, Rossi MH and Pedrosa RC: Inhibition of tumor proliferation associated with cell cycle arrest caused by extract and fraction from Casearia sylvestris (Salicaceae). J Ethnopharmacol. 155:1492–1499. 2014.PubMed/NCBI View Article : Google Scholar

44 

Kaplan EL and Meier P: Nonparametric estimation from incomplete observations. J Am Stat Assoc. 53:457–481. 1958.

45 

Strober W: Trypan blue exclusion test of cell viability. Curr Protoc Immunol 3 (Appendix): 3B, 2001.

46 

Fox K: Drug-DNA interaction protocols. 2nd edition. Humana Press, Southampton, 1977.

47 

Villanueva PJ, Martinez A, Baca ST, DeJesus RE, Larragoity M, Contreras L, Gutierrez DA, Varela-Ramirez A and Aguilera RJ: Pyronaridine exerts potent cytotoxicity on human breast and hematological cancer cells through induction of apoptosis. PLoS One. 13(e0206467)2018.PubMed/NCBI View Article : Google Scholar

48 

Badisa RB, Darling-Reed SF, Joseph P, Cooperwood JS, Latinwo LM and Goodman CB: Selective cytotoxic activities of two novel synthetic drugs on human breast carcinoma MCF-7 cells. Anticancer Res. 29:2993–2996. 2009.PubMed/NCBI

49 

Duchen MR: Contributions of mitochondria to animal physiology: From homeostatic sensor to calcium signalling and cell death. J Physiol. 516:1–17. 1999.PubMed/NCBI View Article : Google Scholar

50 

Tan ML, Ooi JP, Ismail N, Moad AI and Muhammad TS: Programmed cell death pathways and current antitumor targets. Pharm Res. 26:1547–1560. 2009.PubMed/NCBI View Article : Google Scholar

51 

Nakagawa Y, Suzuki T, Ishii H, Ogata A and Nakae D: Mitochondrial dysfunction and biotransformation of β-carboline alkaloids, harmine and harmaline, on isolated rat hepatocytes. Chem Biol Interact. 188:393–403. 2010.PubMed/NCBI View Article : Google Scholar

52 

Brown R: The bcl-2 family of proteins. Br Med Bull. 53:466–477. 1997.PubMed/NCBI View Article : Google Scholar

53 

Luo W, Liu J, Li J, Zhang D, Liu M, Addo JK, Patil S, Zhang L, Yu J, Buolamwini JK, et al: Anti-cancer effects of JKA97 are associated with its induction of cell apoptosis via a Bax-dependent and p53-independent pathway. J Biol Chem. 283:8624–8633. 2008.PubMed/NCBI View Article : Google Scholar

54 

Bai J, Li Y and Zhang G: Cell cycle regulation and anticancer drug discovery. Cancer Biol Med. 14:348–362. 2017.PubMed/NCBI View Article : Google Scholar

55 

Johnson J, Thijssen B, McDermott U, Garnett M, Wessels LFA and Bernards R: Targeting the RB-E2F pathway in breast cancer. Oncogene. 35:4829–4835. 2016.PubMed/NCBI View Article : Google Scholar

56 

Song Y, Kesuma D, Wang J, Deng Y, Duan J, Wang JH and Qi RZ: Specific inhibition of cyclin-dependent kinases and cell proliferation by harmine. Biochem Biophys Res Commun. 317:128–132. 2004.PubMed/NCBI View Article : Google Scholar

57 

Hilgendorf KI, Leshchiner ES, Nedelcu S, Maynard MA, Calo E, Ianari A, Walensky LD and Lees JA: The retinoblastoma protein induces apoptosis directly at the mitochondria. Genes Dev. 27:1003–1015. 2013.PubMed/NCBI View Article : Google Scholar

58 

Surova O and Zhivotovsky B: Various modes of cell death induced by DNA damage. Oncogene. 32:3789–3797. 2013.PubMed/NCBI View Article : Google Scholar

59 

Hurley LH: DNA and its associated processes as targets for cancer therapy. Nat Rev Cancer. 2:188–200. 2002.PubMed/NCBI View Article : Google Scholar

60 

Pagano B, Caterino M, Filosa R and Giancola C: Binding of Harmine Derivatives to DNA: A Spectroscopic Investigation. Molecules. 22(1831)2017.PubMed/NCBI View Article : Google Scholar

61 

Cseh AM, Fábián Z, Sümegi B and Scorrano L: Poly(adenosine diphosphate-ribose) polymerase as therapeutic target: Lessons learned from its inhibitors. Oncotarget. 8:50221–50239. 2017.PubMed/NCBI View Article : Google Scholar

62 

Rojo F, García-Parra J, Zazo S, Tusquets I, Ferrer-Lozano J, Menendez S, Eroles P, Chamizo C, Servitja S, Ramírez-Merino N, et al: Nuclear PARP-1 protein overexpression is associated with poor overall survival in early breast cancer. Ann Oncol. 23:1156–1164. 2012.PubMed/NCBI View Article : Google Scholar

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Spandidos Publications style
Mota NS, Kviecinski MR, Felipe KB, Grinevicius VM, Siminski T, Almeida GM, Zeferino RC, Pich CT, Filho DW, Pedrosa RC, Pedrosa RC, et al: β-carboline alkaloid harmine induces DNA damage and triggers apoptosis by a mitochondrial pathway: study in silico, in vitro and in vivo. Int J Funct Nutr 1: 1, 2020.
APA
Mota, N.S., Kviecinski, M.R., Felipe, K.B., Grinevicius, V.M., Siminski, T., Almeida, G.M. ... Pedrosa, R.C. (2020). β-carboline alkaloid harmine induces DNA damage and triggers apoptosis by a mitochondrial pathway: study in silico, in vitro and in vivo. International Journal of Functional Nutrition, 1, 1. https://doi.org/10.3892/ijfn.2020.1
MLA
Mota, N. S., Kviecinski, M. R., Felipe, K. B., Grinevicius, V. M., Siminski, T., Almeida, G. M., Zeferino, R. C., Pich, C. T., Filho, D. W., Pedrosa, R. C."β-carboline alkaloid harmine induces DNA damage and triggers apoptosis by a mitochondrial pathway: study in silico, in vitro and in vivo". International Journal of Functional Nutrition 1.1 (2020): 1.
Chicago
Mota, N. S., Kviecinski, M. R., Felipe, K. B., Grinevicius, V. M., Siminski, T., Almeida, G. M., Zeferino, R. C., Pich, C. T., Filho, D. W., Pedrosa, R. C."β-carboline alkaloid harmine induces DNA damage and triggers apoptosis by a mitochondrial pathway: study in silico, in vitro and in vivo". International Journal of Functional Nutrition 1, no. 1 (2020): 1. https://doi.org/10.3892/ijfn.2020.1
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Spandidos Publications style
Mota NS, Kviecinski MR, Felipe KB, Grinevicius VM, Siminski T, Almeida GM, Zeferino RC, Pich CT, Filho DW, Pedrosa RC, Pedrosa RC, et al: β-carboline alkaloid harmine induces DNA damage and triggers apoptosis by a mitochondrial pathway: study in silico, in vitro and in vivo. Int J Funct Nutr 1: 1, 2020.
APA
Mota, N.S., Kviecinski, M.R., Felipe, K.B., Grinevicius, V.M., Siminski, T., Almeida, G.M. ... Pedrosa, R.C. (2020). β-carboline alkaloid harmine induces DNA damage and triggers apoptosis by a mitochondrial pathway: study in silico, in vitro and in vivo. International Journal of Functional Nutrition, 1, 1. https://doi.org/10.3892/ijfn.2020.1
MLA
Mota, N. S., Kviecinski, M. R., Felipe, K. B., Grinevicius, V. M., Siminski, T., Almeida, G. M., Zeferino, R. C., Pich, C. T., Filho, D. W., Pedrosa, R. C."β-carboline alkaloid harmine induces DNA damage and triggers apoptosis by a mitochondrial pathway: study in silico, in vitro and in vivo". International Journal of Functional Nutrition 1.1 (2020): 1.
Chicago
Mota, N. S., Kviecinski, M. R., Felipe, K. B., Grinevicius, V. M., Siminski, T., Almeida, G. M., Zeferino, R. C., Pich, C. T., Filho, D. W., Pedrosa, R. C."β-carboline alkaloid harmine induces DNA damage and triggers apoptosis by a mitochondrial pathway: study in silico, in vitro and in vivo". International Journal of Functional Nutrition 1, no. 1 (2020): 1. https://doi.org/10.3892/ijfn.2020.1
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