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.
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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
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.
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.
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.
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.
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.
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.
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.
Chen Z, Knutson E, Kurosky A, Albrecht T. Degradation of p21cip1 in cells productively infected with human cytomegalovirus. J Virol. 2001;75:3613–25.
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.
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.
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.
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.
Cain K, Bratton SB, Cohen GM. The Apaf-1 apoptosome: a large caspase-activating complex. Biochimie. 2002;84:203–14.
Virag L, Szabo C. The therapeutic potential of poly(ADP-ribose) polymerase inhibitors. Pharmacol Rev. 2002;54:375–429.
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.
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.
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.
Leloup L, Wells A. Calpains as potential anti-cancer targets. Expert. 2011;15:309–23.
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.
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.
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.
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.
Lu Q, Mellgren RL. Calpain inhibitors and serine protease inhibitors can produce apoptosis in HL-60 cells. Arch Biochem Biophys. 1996;334:175–81.
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.
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.
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.
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.
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.
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.
Alshatwi AA. Catechin hydrate suppresses MCF-7 proliferation through TP53/Caspase-mediated apoptosis. J Exp Clin Cancer Res. 2010;29:167.
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.
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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
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DOI: https://doi.org/10.1007/s13277-014-1993-y