Skip to main content
Log in

Effects of curine in HL-60 leukemic cells: cell cycle arrest and apoptosis induction

  • Original Paper
  • Published:
Journal of Natural Medicines Aims and scope Submit manuscript

Abstract

Curine is a natural alkaloid isolated from Chondrodendron platyphyllum and it has been reported that this alkaloid has vasodilatory and anti-inflammatory effects. The aim of this study is to analyze the cytotoxic effects of curine in cancer cell lines HL-60, K562, and HT-29, and in primary cultures of peripheral blood mononuclear cells (PBMC). Cells were treated with curine (from 3 to 15 µM) for 24 and 48 h. Cell viability was analyzed by the 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test and flow cytometry with propidium iodide (PI) assay. To assess the type of cell death induced in HL-60, the cell cycle, morphological, and biochemical alterations were analyzed, which were determined by differential staining with acridine orange/ethidium bromide, and annexin V/PI double-labeling and change in mitochondrial membrane potential assays. Curine demonstrated a potent cytotoxic effect on leukemic cell lines (HL-60 and K562). Its cytotoxic effects in HL-60 cells was related to plasma membrane damage and cell cycle arrest at the G1 phase from 43.4 ± 1.0 to 56.7 ± 1.4 % (p < 0.05). Curine (15 μM) also increased the apoptotic cells number by around 60 % in HL-60 cells and caused phosphatidylserine externalization, inducing about 57 % of apoptosis. Moreover, this alkaloid provoked 20 % of mitochondrial membrane depolarization. We conclude that curine presented a cytotoxic effect and induced apoptosis in HL-60 cells. Thus, it can be considered a promising pharmacological drug.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674

    Article  CAS  PubMed  Google Scholar 

  2. Alison MR (2001) Cancer. Encyclopedia of life sciences. Nature Publishing Group, London

    Google Scholar 

  3. Mishra T, Khullar M, Bhatia A (2011) Anticancer potential of aqueous ethanol seed extract of Ziziphus mauritiana against cancer cell lines and Ehrlich ascites carcinoma. Evid Based Complement Alternat Med. pii: 765029. doi:10.1155/2011/765029

  4. Wang L, Liu L, Shi Y, Cao H, Chaturvedi R, Calcutt MW, Hu T, Ren X, Wilson KT, Polk DB, Yan F (2012) Berberine induces caspase-independent cell death in colon tumor cells through activation of apoptosis-inducing factor. PLoS One 7(5):e36418. doi:10.1371/journal.pone.0036418

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Barbosa-Filho JM, da-Cunha EVL, Gray AI (2000) Alkaloids of the menispermaceae. Alkaloids Chem Biol 54:1–190

    Article  CAS  Google Scholar 

  6. Ribeiro-Filho J, Leite FC, Costa HF, Calheiros AS, Torres RC, de Azevedo CT, Martins MA, da Silva Dias C, Bozza PT, Piuvezam MR (2014) Curine inhibits mast cell-dependent responses in mice. J Ethnopharmacol 155:1118–1124

    Article  CAS  PubMed  Google Scholar 

  7. Ribeiro-Filho J, Calheiros AS, Vieira-de-Abreu A, de Carvalho KI, da Silva Mendes D, Melo CB, Martins MA, da Silva Dias C, Piuvezam MR, Bozza PT (2013) Curine inhibits eosinophil activation and airway hyper-responsiveness in a mouse model of allergic asthma. Toxicol Appl Pharmacol 273(1):19–26

    Article  CAS  PubMed  Google Scholar 

  8. Medeiros MA, Pinho JF, De-Lira DP, Barbosa-Filho JM, Araújo DA, Cortes SF, Lemos VS, Cruz JS (2011) Curine, a bisbenzylisoquinoline alkaloid, blocks L-type Ca2+ channels and decreases intracellular Ca2+ transients in A7r5 cells. Eur J Pharmacol 669:100–107

    Article  CAS  PubMed  Google Scholar 

  9. Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65:55–63

    Article  CAS  PubMed  Google Scholar 

  10. Tanner EA, Blute TA, Brachmann CB, McCall K (2011) Bcl-2 proteins and autophagy regulate mitochondrial dynamics during programmed cell death in the Drosophila ovary. Development 138:327–338

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Al-tel TH (2010) Design and synthesis of novel tetrahydro-2H-Pyrano[3,2-c]Pyridazin-3(6H)-one derivatives as potential anticancer agents. Eur J Med Chem 45:5724–5731

    Article  CAS  PubMed  Google Scholar 

  12. Pedram B, Van oeveren A, Mais DE, Marschke KB, Verbost PM, Groen MB, Zhi L (2008) A tissue-selective nonsteroidal progesterone receptor modulator: 7,9-difluoro-5-(3-methylcyclohex-2-enyl)-2,2,4-trimethyl-1,2-dihydrochromeno[3,4-f]quinoline. J Med Chem 51:3696–3699

    Article  CAS  PubMed  Google Scholar 

  13. Sharma M, Agrawal SK, Sharma PR, Chadha BS, Khosla MK, Saxena AK (2010) Cytotoxic and apoptotic activity of essential oil from Ocimum viride towards COLO 205 cells. Food Chem Toxicol 48:336–344

    Article  CAS  PubMed  Google Scholar 

  14. Kroemer G, Galluzzi L, Vandenabeele P, Abrams J, Alnemri ES, Baehrecke EH, Blagosklonny MV, El-deiry WS, Golstein P, Green DR, Hengartner M, Knight RA, Kumar S, Lipton SA, Malorni W, Nuñez G, Peter ME, Tschopp J, Yuan J, Piacentini M, Zhivotovsky B, Melino G; Nomenclature Committee on Cell Death 2009 (2009) Classification of cell death: recommendations of the Nomenclature Committee on Cell Death 2009. Cell Death Differ 16:3–11

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Andrade R, Crisol L, Prado R, Boyano MD, Arluzea J, Aréchaga J (2009) Plasma membrane and nuclear envelope integrity during the blebbing stage of apoptosis: a time-lapse study. Biol Cell 102:25–35

    Article  PubMed  Google Scholar 

  16. Chidambara Murthy KN, Jayaprakasha GK, Patil BS (2012) The natural alkaloid berberine targets multiple pathways to induce cell death in cultured human colon cancer cells. Eur J Pharmacol 688:14–21

    Article  CAS  PubMed  Google Scholar 

  17. Ding YF, Bao YM, An LJ (2005) Progress research of antitumor agents vinblastine analogues. Chin J Pharm 36:424–428

    CAS  Google Scholar 

  18. Lu JJ, Bao JL, Chen XP, Huang M, Wang YT (2012) Alkaloids isolated from natural herbs as the anticancer agents. Evid Based Complement Alternat Med 2012:485042. doi:10.1155/2012/485042

  19. Ehrhardt H, Wachter F, Grunert M, Jeremias I (2013) Cell cycle-arrested tumor cells exhibit increased sensitivity towards TRAIL-induced apoptosis. Cell Death Dis 4:e661. doi:10.1038/cddis.2013.179

  20. Liu JJ, Lin M, Yu JY, Liu B, Bao JK (2011) Targeting apoptotic and autophagic pathways for cancer therapeutics. Cancer Lett 300:105–114

    Article  CAS  PubMed  Google Scholar 

  21. Elumalai P, Gunadharini DN, Senthilkumar K, Banudevi S, Arunkumar R, Benson CS, Sharmila G, Arunakaran J (2012) Induction of apoptosis in human breast cancer cells by nimbolide through extrinsic and intrinsic pathway. Toxicol Lett 215:131–142

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This research was supported by grants from CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico) and CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior).

Conflict of interest

The authors declare no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Demetrius Antônio Machado Araújo.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PDF 121 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Dantas, B.B., Faheina-Martins, G.V., Coulidiati, T.H. et al. Effects of curine in HL-60 leukemic cells: cell cycle arrest and apoptosis induction. J Nat Med 69, 218–223 (2015). https://doi.org/10.1007/s11418-014-0881-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11418-014-0881-5

Keywords

Navigation