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Experimental study of piperlongumine inducing apoptosis of human breast adenoma MDA-MB-231 cells

  • Published:
The Chinese-German Journal of Clinical Oncology

Abstract

Objective

The aim of the study was to investigate the apoptosis induced by piperlongumine on human breast adenoma MDA-MB-231 cells and the mechanism involved.

Methods

Human breast adenoma MDA-MB-231 cells line was cultured in vitro. The inhibitory effect of piperlongumine on the proliferation of human breast adenoma MDA-MB-231 cells was measured by CCK-8 assay. Distribution of cell cycle was analyzed by flow cytometry. The apoptosis rates of MDA-MB-231 cells were measured using Annexin V/PI staining. The flow cytometry with the probe of DCFH-DA was used to detect the intracellular reactive oxygen species levels. Western blot was used to explore the protein expression of Bcl-2 and Bax.

Results

The CCK-8 assay showed that piperlongumine had an inhibiting effect on the proliferation of MDA-MB-231 cells in a concentration- and time-dependent manner. MDA-MB-231 cells were markedly arrested at G0/G1 phase after treatment of piperlongumine. Piperlongumine induced apoptosis of MDA-MB-231 cells obviously. The level of intracellular reactive oxygen species was increased in a dose-dependent manner. The antioxidant N-acetyl-L-cystein inhibited the apoptosis of cells and the level of intracellular reactive oxygen species was also decreased. By Western blot analysis, we found the expression of Bax was up-regulated whereas that of Bcl-2 was down-regulated in a concentration-dependent manner.

Conclusion

Piperlongumine possesses a significant function for inhibiting proliferation, arresting cells at G0/G1 phase and inducing apoptosis of MDA-MB-231 cells, which seems to be associated with the increased generation of intracellular reactive oxygen species as well as the down-regulation of Bcl-2 and up-regulation of Bax.

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References

  1. Lee SE, Park BS, Bayman P, et al. Suppression of ochratoxin biosynthesis by naturally occurring alkaloids. Food Addit Contam, 2007, 24: 391–397.

    Article  PubMed  CAS  Google Scholar 

  2. Rodrigues RV, Lanznaster D, Longhi Balbinot DT, et al. Antinociceptive effect of crude extract, fractions and three alkaloids obtained from fruits of Piper tuberculatum. Biol Pharm Bull, 2009, 32: 1809–1812.

    Article  PubMed  CAS  Google Scholar 

  3. Cícero Bezerra Felipe F, Trajano Sousa Filho J, de Oliveira Souza LE, et al. Piplartine, an amide alkaloid from Piper tuberculatum, presents anxiolytic and antidepressant effects in mice. Phytomedicine, 2007, 14: 605–612.

    Article  PubMed  Google Scholar 

  4. Moraes Jd, Nascimento C, Lopes PO, et al. Schistosoma mansoni: In vitro schistosomicidal activity of piplartine. Exp Parasitol, 2011, 127: 357–364.

    Article  PubMed  Google Scholar 

  5. Fontenele JB, Leal LK, Silveira ER, et al. Antiplatelet effects of piplartine, an alkaloid isolated from Piper tuberculatum: possible involvement of cyclooxygenase blockade and antioxidant activity. J Pharm Pharmacol, 2009, 61: 511–515.

    PubMed  CAS  Google Scholar 

  6. Park BS, Son DJ, Park YH, et al. Antiplatelet effects of acidamides isolated from the fruits of Piper longum L. Phytomedicine, 2007, 14: 853–855.

    Article  PubMed  CAS  Google Scholar 

  7. Bezerra DP, Pessoa C, Moraes MO, et al. In vivo growth inhibition of sarcoma 180 by piperlonguminine, an alkaloid amide from the Piper species. J Appl Toxicol, 2008, 28: 599–607.

    Article  PubMed  CAS  Google Scholar 

  8. Raj L, Ide T, Gurkar AU, et al. Selective killing of cancer cells by a small molecule targeting the stress response to ROS. Nature, 2011, 475: 231–234.

    Article  PubMed  CAS  Google Scholar 

  9. Shi XB, Wang L. Treatment for triple-negative breast cancer. Chinese-German J Clin Oncol, 2012, 11: 539–543.

    Article  CAS  Google Scholar 

  10. Bauer KR, Brown M, Cress RD, et al. Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype: a population-based study from the California cancer Registry. Cancer, 2007, 109: 1721–1728.

    Article  PubMed  Google Scholar 

  11. Bezerra DP, Militão GC, de Castro FO, et al. Piplartine induces inhibition of leukemia cell proliferation triggering both apoptosis and necrosis pathways. Toxicol In Vitro, 2007, 21: 1–8.

    Article  PubMed  CAS  Google Scholar 

  12. Bezerra DP, Pessoa C, de Moraes MO, et al. Antiproliferative effects of two amides, piperine and piplartine, from Piper species. Z Naturforsch C, 2005, 60: 539–543.

    PubMed  CAS  Google Scholar 

  13. Jyothi D, Vanathi P, Mangala Gowri P, et al. Diferuloylmethane augments the cytotoxic effects of piplartine isolated from Piper chaba. Toxicol In Vitro, 2009, 23: 1085–1091.

    Article  PubMed  CAS  Google Scholar 

  14. Kong EH, Kim YJ, Kim YJ, et al. Piplartine induces caspase-mediated apoptosis in PC-3 human prostate cancer cells. Oncol Rep, 2008, 20: 785–792.

    PubMed  CAS  Google Scholar 

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Correspondence to Yongbiao Liu.

Additional information

Supported by grants from the Priority Academic Program Development of Jiangsu Higher Education Institutions (No. JX10231801) and the Innovative Medical Team and Leading Talent of Jiangsu Province (No. LJ201123).

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Yao, Z., Yao, J., He, X. et al. Experimental study of piperlongumine inducing apoptosis of human breast adenoma MDA-MB-231 cells. Chin. -Ger. J. Clin. Oncol. 12, 319–325 (2013). https://doi.org/10.1007/s10330-013-1144-8

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  • DOI: https://doi.org/10.1007/s10330-013-1144-8

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