title: Sanguinarine induces apoptosis in human colorectal cancer HCT-116 cells through ROS-mediated Egr-1 activation and mitochondrial dysfunction.
abstract: We examined the effects of sanguinarine, a benzophenanthridine alkaloid, on reactive oxygen species (ROS) production and the association of these effects with apoptotic cell death in a human colorectal cancer HCT-116 cell line. Sanguinarine generated ROS, which was followed by a decrease in the mitochondrial membrane potential (MMP), the activation of caspase-9 and -3, and the down-regulation of anti-apoptotic proteins, such as Bcl2, XIAP and cIAP-1. Sanguinarine also promoted the activation of caspase-8 and truncation of Bid (tBid). However, the quenching of ROS generation by N-acetyl-l-cysteine, a scavenger of ROS, reversed the sanguinarine-induced apoptosis effects via inhibition of the MMP collapse, tBid expression, and activation of caspases. Sanguinarine also markedly induced the expression of the early growth response gene-1 (Egr-1) during the early period, after which expression level was decreased. In addition, HCT-116 cells transfected with Egr-1 siRNA displayed significant blockage of sanguinarine-induced apoptotic activity in a ROS-dependent manner. These observations clearly indicate that ROS, which are key mediators of Egr-1 activation and MMP collapse, are involved in the early molecular events in the sanguinarine-induced apoptotic pathway acting in HCT-116 cells.
authors: Department of Biomaterial Control (BK21 Program), Graduate School, Dongeui University, Busan 614-714, Republic of Korea.
authors: Min Ho
authors: MH
authors: Han
authors: Gi-Young
authors: GY
authors: Kim
authors: Young Hyun
authors: YH
authors: Yoo
authors: Yung Hyun
authors: YH
authors: Choi
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053119:Benzophenanthridines / Q000494:pharmacology*; D020169:Caspases / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051766:Early Growth Response Protein 1 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D045325:HCT116 Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D007546:Isoquinolines / Q000494:pharmacology*; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection
chemical_list: D053119:Benzophenanthridines; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D051034:Inhibitor of Apoptosis Proteins; D007546:Isoquinolines; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; C005705:sanguinarine; D020169:Caspases; D020782:Matrix Metalloproteinases