Anti-colon cancer effects of Salograviolide A isolated from Centaurea ainetensis.
The antitumor activity of extracts of Centaurea ainetensis (C. ainetensis), a plant endemic to Lebanon, was investigated in human colon carcinoma cells. At concentrations that were non-cytotoxic to normal human intestinal epithelial cells, the crude extract inhibited the proliferation of a host of colon-derived cancer cells. The crude extract effect was then investigated in HCT-116 (p53+/+) cells, most sensitive to treatment and was found to cause apoptosis, increase the Bax/Bcl-2 ratio, p53 and p21 protein levels and reduce cyclin B1 proteins. In vivo, the crude extract injected intraperitoneally before the subcutaneous injection of the carcinogen 1,2-dimethylhydrazine, drastically reduced the number of tumors and decreased the mean size of aberrant crypt foci. Further bioassay-guided fractionation of the crude extract resulted in the identification of the bioactive molecule Salograviolide A, a Sesquiterpene Lactone, to which the growth inhibition in colon cancer was linked. Salograviolide A, at non-cytotoxic concentrations to normal human intestinal cells, reduced the growth of colon cancer cell lines. Salograviolide A induced growth inhibition and resulted in an increased preG1 phase and presumably apoptosis induction which was further confirmed by TUNEL. These data support the testing of the C. ainetensis extract and its bioactive molecule, Salograviolide A, in colon cancer treatment.
El-Najjar
Nahed
N
Department of Biology, American University of Beirut, Beirut 1107 2020, Lebanon.
Dakdouki
Saadah
S
Darwiche
Nadine
N
El-Sabban
Marwan
M
Saliba
Najat A
NA
Gali-Muhtasib
Hala
H
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D031179:Centaurea / Q000737:chemistry*; D003110:Colonic Neoplasms / Q000188:drug therapy*; D006575:Heterocyclic Compounds, 3-Ring / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008517:Phytotherapy; D010936:Plant Extracts / Q000032:analysis / Q000494:pharmacology* / Q000627:therapeutic use
D000972:Antineoplastic Agents, Phytogenic; D006575:Heterocyclic Compounds, 3-Ring; D010936:Plant Extracts; C528991:salograviolide A