Naturally occurring lignans efficiently induce apoptosis in colorectal tumor cells.
Plant-derived lignans caused cell loss by apoptosis in colorectal adenoma and carcinoma cells. Nordihydroguaiaretic acid (NDGA), commonly used for the inhibition of lipoxygenase isoenzymes, showed the strongest growth inhibition with an IC50 of 1.9+/-0.5 microg followed by epiashantin (IC50=9.8+/-4.5 microM) and arctigenin (IC50=16.5+/-8.5 microM). The lignans caused a time- and dose-dependent loss of mitochondrial membrane potential (MMP), down regulation of the anti-apoptotic protein bcl(xl) and an increase of the apoptotic index. The time interval until loss of MMP and down modulation of bcl(xl) became evident correlated with the efficiency of growth inhibition by NDGA, epiashantin and yangambin. Bcl2 and caspase 3 were not involved. NDGA also induced a shift of the culture population to the G2/M phase of the cell cycle. With respect to these results, naturally occurring lignans could be useful in the therapy and chemoprevention of colorectal tumors.
Hausott
B
B
Institute of Cancer Research, University of Vienna, Borschkegasse 8a, 1090, Vienna, Austria.
Greger
H
H
Marian
B
B
D000236:Adenoma / Q000188:drug therapy / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002277:Carcinoma / Q000188:drug therapy / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D020128:Inhibitory Concentration 50; D007413:Intestinal Mucosa / Q000187:drug effects; D017705:Lignans / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D016859:Lipoxygenase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D009637:Masoprocol / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D018514:Plant Structures; D010946:Plants, Medicinal; D051381:Rats
D017705:Lignans; D016859:Lipoxygenase Inhibitors; D010936:Plant Extracts; D009637:Masoprocol