Berberine Induces Caspase-Independent Cell Death in Colon Tumor Cells through Activation of Apoptosis-Inducing Factor
| Autor: | Tianhui Hu, Liping Liu, Lihong Wang, Xiubao Ren, Rupesh Chaturvedi, Keith T. Wilson, M. Wade Calcutt, Hanwei Cao, D. Brent Polk, Yan Shi, Fang Yan |
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| Rok vydání: | 2012 |
| Předmět: |
Phytochemistry
Necrosis Berberine Phytopharmacology lcsh:Medicine Biochemistry Cathepsin B Mice chemistry.chemical_compound 0302 clinical medicine Drug Discovery Molecular Cell Biology Gastrointestinal Cancers Signaling in Cellular Processes lcsh:Science Caspase Apoptotic Signaling Cellular Stress Responses 0303 health sciences Multidisciplinary Cell Death biology Apoptosis Inducing Factor Mitochondria 3. Good health Cell biology Mitotic Signaling Chemistry Caspases 030220 oncology & carcinogenesis Colonic Neoplasms Medicine Poly(ADP-ribose) Polymerases medicine.symptom Research Article Signal Transduction Programmed cell death Poly ADP ribose polymerase Active Transport Cell Nucleus Antineoplastic Agents Gastroenterology and Hepatology Cell Growth 03 medical and health sciences Cell Line Tumor medicine Animals Humans Biology 030304 developmental biology Cell Nucleus L-Lactate Dehydrogenase lcsh:R Epithelial Cells Cas Signaling chemistry Apoptosis Cell culture biology.protein lcsh:Q Reactive Oxygen Species |
| Zdroj: | PLoS ONE, Vol 7, Iss 5, p e36418 (2012) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Berberine, an isoquinoline alkaloid derived from plants, is a traditional medicine for treating bacterial diarrhea and intestinal parasite infections. Although berberine has recently been shown to suppress growth of several tumor cell lines, information regarding the effect of berberine on colon tumor growth is limited. Here, we investigated the mechanisms underlying the effects of berberine on regulating the fate of colon tumor cells, specifically the mouse immorto-Min colonic epithelial (IMCE) cells carrying the Apc(min) mutation, and of normal colon epithelial cells, namely young adult mouse colonic epithelium (YAMC) cells. Berberine decreased colon tumor colony formation in agar, and induced cell death and LDH release in a time- and concentration-dependent manner in IMCE cells. In contrast, YAMC cells were not sensitive to berberine-induced cell death. Berberine did not stimulate caspase activation, and PARP cleavage and berberine-induced cell death were not affected by a caspase inhibitor in IMCE cells. Rather, berberine stimulated a caspase-independent cell death mediator, apoptosis-inducing factor (AIF) release from mitochondria and nuclear translocation in a ROS production-dependent manner. Amelioration of berberine-stimulated ROS production or suppression of AIF expression blocked berberine-induced cell death and LDH release in IMCE cells. Furthermore, two targets of ROS production in cells, cathepsin B release from lysosomes and PARP activation were induced by berberine. Blockage of either of these pathways decreased berberine-induced AIF activation and cell death in IMCE cells. Thus, berberine-stimulated ROS production leads to cathepsin B release and PARP activation-dependent AIF activation, resulting in caspase-independent cell death in colon tumor cells. Notably, normal colon epithelial cells are less susceptible to berberine-induced cell death, which suggests the specific inhibitory effects of berberine on colon tumor cell growth. |
| Databáze: | OpenAIRE |
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