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Crataegus azarolus Leaves Induce Antiproliferative Activity, Cell Cycle Arrest, and Apoptosis in Human HT-29 and HCT-116 Colorectal Cancer Cells.
J Cell Biochem. 2016 May; 117(5):1262-72.JC

Abstract

Limited success has been achieved in extending the survival of patients with metastatic colorectal cancer (CRC). There is a strong need for novel agents in the treatment and prevention of CRC. Therefore, in the present study we evaluated the antiproliferative and pro-apoptotic potential of Crataegus azarolus ethyl acetate extract in HCT-116 and HT-29 human colorectal cancer cell lines. Moreover, we attempted to investigate the signaling pathways that should be involved in its cytotoxic effect. The Crataegus azarolus ethyl acetate extract-induced growth inhibitory effect was associated with DNA fragmentation, sub-G1 peak, loss of mitochondrial potential, and poly (ADP-ribose) polymerase (PARP) cleavage. In addition, ethyl acetate extract of Crataegus azarolus induced the cleavage of caspase-8. It has no effect on steady-state levels of total Bcl-2 protein. Whereas Bax levels decreased significantly in a dose-dependent manner in both tested cell lines. Taken together, these findings confirm the involvement of the extrinsic pathway of apoptosis. The apoptotic cell death induced by ethyl acetate extract of Crataegus azarolus was accompanied by an enhancement of the p21 expression but not through p53 activation in human colorectal cancer cells. The above-mentioned data provide insight into the molecular mechanisms of Crataegus azarolus ethyl acetate extract-induced apoptosis in CRC. Therefore, this compound should be a potential anticancer agent for the treatment of CRC.

Authors+Show Affiliations

Laboratoire de biologie cellulaire et moléculaire, Faculté de médecine dentaire, Université de Monastir, Rue Avicenne, 5000, Monastir, Tunisie. Unité de Substances naturelles bioactives et biotechnologie UR12ES12, Faculté de pharmacie de Monastir, Université de Monastir, Rue Avicenne, 5000, Monastir, Tunisie.Laboratoire de Chimie des Substances Naturelles, EA 1069, Faculté de Pharmacie, Université de Limoges, 2 rue du Dr marcland, 87025, Limoges, France.Laboratoire de Chimie des Substances Naturelles, EA 1069, Faculté de Pharmacie, Université de Limoges, 2 rue du Dr marcland, 87025, Limoges, France.Laboratoire de Chimie des Substances Naturelles, EA 1069, Faculté de Pharmacie, Université de Limoges, 2 rue du Dr marcland, 87025, Limoges, France.Unité de Substances naturelles bioactives et biotechnologie UR12ES12, Faculté de pharmacie de Monastir, Université de Monastir, Rue Avicenne, 5000, Monastir, Tunisie.Laboratoire de Pharmacognosie, E.A. 4481, Faculté de Pharmacie B.P. 83, Université de Lille 2, 59006, Lille cedex, France.Laboratoire de biologie cellulaire et moléculaire, Faculté de médecine dentaire, Université de Monastir, Rue Avicenne, 5000, Monastir, Tunisie. Unité de Substances naturelles bioactives et biotechnologie UR12ES12, Faculté de pharmacie de Monastir, Université de Monastir, Rue Avicenne, 5000, Monastir, Tunisie.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26495895

Citation

Mustapha, Nadia, et al. "Crataegus Azarolus Leaves Induce Antiproliferative Activity, Cell Cycle Arrest, and Apoptosis in Human HT-29 and HCT-116 Colorectal Cancer Cells." Journal of Cellular Biochemistry, vol. 117, no. 5, 2016, pp. 1262-72.
Mustapha N, Pinon A, Limami Y, et al. Crataegus azarolus Leaves Induce Antiproliferative Activity, Cell Cycle Arrest, and Apoptosis in Human HT-29 and HCT-116 Colorectal Cancer Cells. J Cell Biochem. 2016;117(5):1262-72.
Mustapha, N., Pinon, A., Limami, Y., Simon, A., Ghedira, K., Hennebelle, T., & Chekir-Ghedira, L. (2016). Crataegus azarolus Leaves Induce Antiproliferative Activity, Cell Cycle Arrest, and Apoptosis in Human HT-29 and HCT-116 Colorectal Cancer Cells. Journal of Cellular Biochemistry, 117(5), 1262-72. https://doi.org/10.1002/jcb.25416
Mustapha N, et al. Crataegus Azarolus Leaves Induce Antiproliferative Activity, Cell Cycle Arrest, and Apoptosis in Human HT-29 and HCT-116 Colorectal Cancer Cells. J Cell Biochem. 2016;117(5):1262-72. PubMed PMID: 26495895.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Crataegus azarolus Leaves Induce Antiproliferative Activity, Cell Cycle Arrest, and Apoptosis in Human HT-29 and HCT-116 Colorectal Cancer Cells. AU - Mustapha,Nadia, AU - Pinon,Aline, AU - Limami,Youness, AU - Simon,Alain, AU - Ghedira,Kamel, AU - Hennebelle,Thierry, AU - Chekir-Ghedira,Leila, Y1 - 2015/11/05/ PY - 2015/02/19/received PY - 2015/10/21/accepted PY - 2015/10/27/entrez PY - 2015/10/27/pubmed PY - 2016/12/15/medline KW - APOPTOSIS KW - CASPASE-8 KW - COLORECTAL CANCER CELLS KW - CRATAEGUS AZAROLUS KW - P21 KW - PARP SP - 1262 EP - 72 JF - Journal of cellular biochemistry JO - J Cell Biochem VL - 117 IS - 5 N2 - Limited success has been achieved in extending the survival of patients with metastatic colorectal cancer (CRC). There is a strong need for novel agents in the treatment and prevention of CRC. Therefore, in the present study we evaluated the antiproliferative and pro-apoptotic potential of Crataegus azarolus ethyl acetate extract in HCT-116 and HT-29 human colorectal cancer cell lines. Moreover, we attempted to investigate the signaling pathways that should be involved in its cytotoxic effect. The Crataegus azarolus ethyl acetate extract-induced growth inhibitory effect was associated with DNA fragmentation, sub-G1 peak, loss of mitochondrial potential, and poly (ADP-ribose) polymerase (PARP) cleavage. In addition, ethyl acetate extract of Crataegus azarolus induced the cleavage of caspase-8. It has no effect on steady-state levels of total Bcl-2 protein. Whereas Bax levels decreased significantly in a dose-dependent manner in both tested cell lines. Taken together, these findings confirm the involvement of the extrinsic pathway of apoptosis. The apoptotic cell death induced by ethyl acetate extract of Crataegus azarolus was accompanied by an enhancement of the p21 expression but not through p53 activation in human colorectal cancer cells. The above-mentioned data provide insight into the molecular mechanisms of Crataegus azarolus ethyl acetate extract-induced apoptosis in CRC. Therefore, this compound should be a potential anticancer agent for the treatment of CRC. SN - 1097-4644 UR - https://www.unboundmedicine.com/medline/citation/26495895/Crataegus_azarolus_Leaves_Induce_Antiproliferative_Activity_Cell_Cycle_Arrest_and_Apoptosis_in_Human_HT_29_and_HCT_116_Colorectal_Cancer_Cells_ L2 - https://doi.org/10.1002/jcb.25416 DB - PRIME DP - Unbound Medicine ER -