6-methoxydihydrosanguinarine and Colonic-Neoplasms

6-methoxydihydrosanguinarine (6ME), a benzophenanthridine alkaloid derived from the methanol extracts of Hylomecon hylomeconoides, showed a dose-dependent effect at 1-10 microM on causing apoptotic cell death in HT29 colon carcinoma cells (IC50 = 5.0+/-0.2 microM). Treatment of HT-29 cells with 6ME resulted in the formation of internucleosomal DNA fragmentation. Treatment of the cells with 6ME caused activation of caspase-3, -8 and 9 protease and subsequent proteolytic cleavage of poly(ADP-ribose)polymerase. 6ME increased the expression of p53 and Bax and decreased the expression of Bid. These results indicate that p53 and proapoptotic Bcl-2 family proteins might participate in the antiproliferative activity of 6ME in HT29 cells.

Topics: Alkaloids; Antineoplastic Agents, Phytogenic; Apoptosis; Benzophenanthridines; Cell Proliferation; Colonic Neoplasms; Colorectal Neoplasms; Growth Inhibitors; HT29 Cells; Humans; Isoquinolines; Phenanthridines; Plant Extracts