Crataegus azarolus Leaves Induce Antiproliferative Activity, Cell Cycle Arrest, and Apoptosis in Human HT-29 and HCT-116 Colorectal Cancer Cells.
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.
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.
Nadia
N
Mustapha
Laboratoire de Chimie des Substances Naturelles, EA 1069, Faculté de Pharmacie, Université de Limoges, 2 rue du Dr marcland, 87025, Limoges, France.
Aline
A
Pinon
Laboratoire de Chimie des Substances Naturelles, EA 1069, Faculté de Pharmacie, Université de Limoges, 2 rue du Dr marcland, 87025, Limoges, France.
Youness
Y
Limami
Laboratoire de Chimie des Substances Naturelles, EA 1069, Faculté de Pharmacie, Université de Limoges, 2 rue du Dr marcland, 87025, Limoges, France.
Alain
A
Simon
Unité de Substances naturelles bioactives et biotechnologie UR12ES12, Faculté de pharmacie de Monastir, Université de Monastir, Rue Avicenne, 5000, Monastir, Tunisie.
Kamel
K
Ghedira
Laboratoire de Pharmacognosie, E.A. 4481, Faculté de Pharmacie B.P. 83, Université de Lille 2, 59006, Lille cedex, France.
Thierry
T
Hennebelle
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.
Leila
L
Chekir-Ghedira
D000085:Acetates / Q000737:chemistry; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053181:Caspase 8 / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D027825:Crataegus / Q000737:chemistry*; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008856:Microscopy, Fluorescence; D010936:Plant Extracts / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry*; D000071137:Poly (ADP-Ribose) Polymerase-1 / Q000378:metabolism
D000085:Acetates; D000970:Antineoplastic Agents; D010936:Plant Extracts; C007650:ethyl acetate; D000071137:Poly (ADP-Ribose) Polymerase-1; D053181:Caspase 8
APOPTOSIS; CASPASE-8; COLORECTAL CANCER CELLS; CRATAEGUS AZAROLUS; P21; PARP