Onopordum cynarocephalum induces apoptosis and protects against 1,2 dimethylhydrazine-induced colon cancer.
The potential chemopreventive properties of the crude extract of Onopordum cynarocephalum were evaluated. Growth inhibition was investigated in FHs74Int human normal intestinal cells and ModeK mouse normal intestinal cell line and in two human colon cancer cells HCT-116 (p53+/+) and HT-29 (p53+/-). The extract was not cytotoxic to FHs74Int cells at concentrations 2-fold higher than the IC50 of HCT-116 cells. The extract inhibited dose-dependently the growth of HCT-116 cells (IC50=0.18 mg/ml) to a greater extent than HT-29 cells (IC50=1.8 mg/ml). The p53 wild-type HCT-116 cells were more sensitive than p53 mutant HT-29 cells to the pro-apoptotic effects of the plant extract; five times lower concentrations were needed to induce apoptosis in HCT-116 cells. Apoptosis induction by the extract was associated with an increase in the expression of pro-apoptotic proteins such as p53 and Bax, and a significant inhibition of the anti-apoptotic protein Bcl-2. Significant decrease in cyclin D1 protein and increase in p21 protein was observed in extract-treated HCT-116 cells. In vivo, the crude extract injected intra-peritoneally reduced the number of tumors by 64% (p<0.0001) and decreased the mean size of aberrant crypt foci in the DMH model of colon cancer. These data collectively suggest that O. cynarocephalum has potential anti-colon cancer effects.
El-Najjar
Nahed
N
Department of Biology, American University of Beirut, Beirut, Lebanon.
Saliba
Najat
N
Talhouk
Salma
S
Gali-Muhtasib
Hala
H
D019813:1,2-Dimethylhydrazine / Q000633:toxicity; D000818:Animals; D017209:Apoptosis; D002273:Carcinogens / Q000633:toxicity; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D031183:Onopordum / Q000737:chemistry*; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D002273:Carcinogens; D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D019813:1,2-Dimethylhydrazine