Apoptosis inducing effects of 6-methoxydihydrosanguinarine in HT29 colon carcinoma cells.
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.
Lee
Yong-Jin
YJ
College of Pharmacy and MeRRI, Wonkwang University, Iksan 570-749, Korea.
Yin
Hu-Quan
HQ
Kim
Young-Ho
YH
Li
Guang-Yong
GY
Lee
Byung-Hoon
BH
D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D053119:Benzophenanthridines; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000473:pathology*; D006131:Growth Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D019073:HT29 Cells; D006801:Humans; D007546:Isoquinolines; D010617:Phenanthridines / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology
C438021:6-methoxydihydrosanguinarine; D000470:Alkaloids; D000972:Antineoplastic Agents, Phytogenic; D053119:Benzophenanthridines; D006131:Growth Inhibitors; D007546:Isoquinolines; D010617:Phenanthridines; D010936:Plant Extracts