Skip to main content

Advertisement

Log in

Limoniastrum guyonianum aqueous gall extract induces apoptosis in colorectal cancer cells by inhibiting calpain activity

  • Research Article
  • Published:
Tumor Biology

Abstract

Several studies have reported that plant-derived natural products have cancer chemopreventive and chemotherapeutic properties. The aim of the present study was to determine the antiproliferative and pro-apoptotic potential of Limoniastrum guyonianum aqueous gall extract (G extract) on human colorectal cancer BE cell line and, if so, to characterize the mechanism involved. The G extract-induced growth inhibitory effect was associated with an arrest of cell cycle progression in G2/M phase as shown by the cell phase distribution. In addition, G extract promoted in a concentration-dependent manner these cells towards apoptosis as indicated by the presence of cleaved poly(ADP-ribose) polymerase (PARP). In order to characterize the mechanism involved in the antiproliferative and pro-apoptotic signaling pathway activated by G extract, calpain activity and the expression of the cell cycle inhibitor p16INK4A were determined. The present findings indicated that G extract exhibited significant inhibitory activity against calpain and caused a marked and concentration-dependent upregulation of p16INK4A. These effects could be ascribed to the presence of condensed tannins and polyphenols such as epicatechin and epigallocatechin gallate in G extract.

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
Fig. 5
Fig. 6

Similar content being viewed by others

Abbreviations

G extract:

Aqueous gall extract

DMSO:

Dimethylsulfoxide

TBS:

Tris-buffered saline

GAPDH:

Glyceraldehyde 3-phosphate dehydrogenase

MALDI-TOF:

Matrix-assisted laser desorption/ionization-time of flight

References

  1. Sabatino L, Fucci A, Pancione M, Carafa V, Nebbioso A, Pistore C, et al. UHRF1 coordinates peroxisome proliferator activated receptor gamma (PPARG) epigenetic silencing and mediates colorectal cancer progression. Oncogene. 2012;31(49):5061–72.

    Article  CAS  PubMed  Google Scholar 

  2. Krifa M, Bouhlel I, Ghedira-Chekir L, Ghedira K. Immunomodulatory and cellular anti-oxidant activities of an aqueous extract of Limoniastrum guyonianum gall. J Ethnopharmacol. 2013;146:243–9.

    Article  CAS  PubMed  Google Scholar 

  3. Krifa M, Bouhlel I, Skandrani I, Chekir L. Ghedira k. Antioxidant, mutagenic and antimutagenic activities of an aqueous extract of Limoniastrum guyonianum Gall. Drug Chem Toxicol. 2013;37(1):76–82.

    Article  PubMed  Google Scholar 

  4. Krifa M, Alhosin M, Muller CD, Gies JP, Chekir-Ghedira L, Ghedira K, et al. Limoniastrum guyonianum aqueous gall extract induces apoptosis in human cervical cancer cells involving p16INK4A re-expression related to UHRF1 and DNMT1 down-regulation. J Exp Clin Cancer Res. 2013;32:30.

    Article  PubMed Central  PubMed  Google Scholar 

  5. Janossy J, Ubezio P, Apati A, Magocsi M, Tompa P, Friedrich P. Calpain as a multi-site regulator of cell cycle. Biochem Pharmacol. 2004;67:1513–21.

    Article  CAS  PubMed  Google Scholar 

  6. Choi YH, Lee SJ, Nguyen P, Jang JS, Lee J, Wu M-L, et al. Regulation of cyclin D1 by calpain protease. J Biol Chem. 1997;272:28479–84.

    Article  CAS  PubMed  Google Scholar 

  7. Wang XD, Rosales JL, Magliocco A, Gnanakumar R, Lee KY. Cyclin E in breast tumors is cleaved into its low molecular weight forms by calpain. Oncogene. 2003;22:769–74.

    Article  CAS  PubMed  Google Scholar 

  8. Chen Z, Knutson E, Kurosky A, Albrecht T. Degradation of p21cip1 in cells productively infected with human cytomegalovirus. J Virol. 2001;75:3613–25.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Delmas C, Aragou N, Poussard S, Cottin P, Darbon JM, Manenti S. MAP kinase-dependent degradation of p27Kip1 by calpains in choroidal melanoma cells. Requirement of p27Kip1 nuclear export. J Biol Chem. 2003;278:12443–51.

    Article  CAS  PubMed  Google Scholar 

  10. Abusnina A, Keravis T, Yougbare I, Bronner C, Lugnier C. Anti-proliferative effect of curcumin on melanoma cells is mediated by PDE1A inhibition that regulates the epigenetic integrator UHRF1. Mol Nutr Food Res. 2011;55(11):1677–89.

    Article  CAS  PubMed  Google Scholar 

  11. Pasch H, Rode K, Ghahary R, Braun D. Matrix-assisted laser desorption/ionization mass spectrometry of synthetic polymers. Part 3. Analysis of condensation polymers. Angew Makromol Chem. 1996;95:241.

    Google Scholar 

  12. Alhosin M, Sharif T, Mousli M, Etienne-Selloum N, Fuhrmann G, Schini-Kerth VB, et al. Down-regulation of UHRF1, associated with re-expression of tumor suppressor genes, is a common feature of natural compounds exhibiting anti-cancer properties. J Exp Clin Cancer Res. 2011;15(30):41.

    Article  Google Scholar 

  13. Cain K, Bratton SB, Cohen GM. The Apaf-1 apoptosome: a large caspase-activating complex. Biochimie. 2002;84:203–14.

    Article  CAS  PubMed  Google Scholar 

  14. Virag L, Szabo C. The therapeutic potential of poly(ADP-ribose) polymerase inhibitors. Pharmacol Rev. 2002;54:375–429.

    Article  CAS  PubMed  Google Scholar 

  15. Jin H, Gong W, Zhang C, Wang S. Epigallocatechin gallate inhibits the proliferation of colorectal cancer cells by regulating Notch signaling. Onco. 2013;6:145–53.

    CAS  Google Scholar 

  16. Etebari M, Zolfaghari B, Jafarian-Dehkordi A, Rakian R. Evaluation of DNA damage of hydro-alcoholic and aqueous extract of Echium amoenum and Nardostachys jatamansi. J Res Med Sci. 2012;17:782–6.

    CAS  PubMed Central  PubMed  Google Scholar 

  17. Kilani-Jaziri S, Frachet V, Bhouri W, Ghedira K, Chekir-Ghedira L, Ronot X. Flavones inhibit the proliferation of human tumor cancer cell lines by inducing apoptosis. Drug. 2011;35:1–10.

    CAS  Google Scholar 

  18. Leloup L, Wells A. Calpains as potential anti-cancer targets. Expert. 2011;15:309–23.

    CAS  Google Scholar 

  19. Mellgren RL. Evidence for participation of a calpain-like cysteine protease in cell cycle progression through late G1 phase. Biochem Biophys Res Commun. 1997;236:555–8.

    Article  CAS  PubMed  Google Scholar 

  20. Joy J, Nalabothula N, Ghosh M, Popp O, Jochum M, Machleidt W, et al. Identification of calpain cleavage sites in the G1 cyclin-dependent kinase inhibitor p19(INK4d). Biol Chem. 2006;387:329–35.

    Article  CAS  PubMed  Google Scholar 

  21. Je Ma C, Jung WJ, Lee KY, Kim YC, Sung SH. Calpain inhibitory flavonoids isolated from Orostachys japonicus. J Enzyme Inhib Med Chem. 2009;24:676–9.

    Article  PubMed  Google Scholar 

  22. Kim JK, Esteve PO, Jacobsen SE, Pradhan S. UHRF1 binds G9a and participates in p21 transcriptional regulation in mammalian cells. Nucleic Acids Res. 2009;37:493–505. doi:10.1093/nar/gkn961.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Lu Q, Mellgren RL. Calpain inhibitors and serine protease inhibitors can produce apoptosis in HL-60 cells. Arch Biochem Biophys. 1996;334:175–81.

    Article  CAS  PubMed  Google Scholar 

  24. Knepper-Nicolai B, Savill J, Brown SB. Constitutive apoptosis in human neutrophils requires synergy between calpains and the proteasome downstream of caspases. J Biol Chem. 1998;273:30530–6.

    Article  CAS  PubMed  Google Scholar 

  25. Zhang C, Siman R, Xu YA, Mills AM, Frederick JR, Neumar RW. Comparison of calpain and caspase activities in the adult rat brain after transient forebrain ischemia. Neurobiol Dis. 2002;10:289–05.

    Article  CAS  PubMed  Google Scholar 

  26. Bao JJ, Le XF, Wang RY, Yuan J, Wang L, Atkinson EN, et al. Reexpression of the tumor suppressor gene ARHI induces apoptosis in ovarian and breast cancer cells through a caspase-independent calpain-dependent pathway. Cancer Res. 2002;62:7264–72.

    CAS  PubMed  Google Scholar 

  27. Nath R, Raser KJ, Stafford D, Hajimohammadreza I, Posner A, Allen H, et al. Non-erythroid alpha-spectrin breakdown by calpain and interleukin 1 beta-converting-enzyme-like protease(s) in apoptotic cells: contributory roles of both protease families in neuronal apoptosis. Biochem J. 1996;319:683–90.

    CAS  PubMed Central  PubMed  Google Scholar 

  28. Zhu DM, Uckun FM. Calpain inhibitor II induces caspase-dependent apoptosis in human acute lymphoblastic leukemia and non-Hodgkin’s lymphoma cells as well as some solid tumor cells. Clin Cancer Res. 2000;6:2456–63.

    CAS  PubMed  Google Scholar 

  29. Guan N, Korukonda R, Hurh E, Schmittgen TD, Donkor IO, Dalton JT. Apoptosis induced by novel aldehyde calpain inhibitors in human tumor cell lines. Int J Oncol. 2006;29:655–63.

    CAS  PubMed  Google Scholar 

  30. Alshatwi AA. Catechin hydrate suppresses MCF-7 proliferation through TP53/Caspase-mediated apoptosis. J Exp Clin Cancer Res. 2010;29:167.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Achour M, Mousli M, Alhosin M, Ibrahim A, Peluso J, Muller CD, et al. Epigallocatechin-3-gallate up-regulates tumor suppressor gene expression via a reactive oxygen species-dependent down-regulation of UHRF1. Biochem Biophys Res Commun. 2012;430(1):208–12.

    Article  PubMed  Google Scholar 

Download references

Conflict of interest

None

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Leila Chekir-Ghedira.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Krifa, M., Pizzi, A., Mousli, M. et al. Limoniastrum guyonianum aqueous gall extract induces apoptosis in colorectal cancer cells by inhibiting calpain activity. Tumor Biol. 35, 7877–7885 (2014). https://doi.org/10.1007/s13277-014-1993-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-014-1993-y

Keywords

Navigation