https://scholars.lib.ntu.edu.tw/handle/123456789/307470
Title: | Induction of apoptosis by shikonin through coordinative modulation of the Bcl-2 family, p27, and p53, release of cytochrome c, and sequential activation of caspases in human colorectal carcinoma cells | Authors: | Hsu, P.-C. Huang, Y.-T. Tsai, M.-L. Wang, Y.-J. Lin, J.-K. MIN-HSIUNG PAN |
Keywords: | Apoptosis; Bcl-2; Bcl-XL; Caspase-3; Caspase-9; Caspase-activated deoxyribonuclease; Cytochrome c; DNA fragmentation factor; Poly-(ADP-ribose) polymerase; Shikonin | Issue Date: | 2004 | Journal Volume: | 52 | Journal Issue: | 20 | Start page/Pages: | 6330-6337 | Source: | Journal of Agricultural and Food Chemistry | Abstract: | Shikonin is a main constituent of the roots of Lithospermum erythrorhizon that has antimutagenic activity. However, its other biological activities are not well-known. Shikonin displayed a strong inhibitory effect against human colorectal carcinoma COLO 205 cells and human leukemia HL-60 cells, with estimated IC50 values of 3.12 and 5.5 μM, respectively, but were less effective against human colorectal carcinoma HT-29 cells, with an estimated IC50 value of 14.8 μM. Induce apoptosis was confirmed in COLO 205 cells by DNA fragmentation and the appearance of a sub-G1 DNA peak, which were preceded by loss of mitochondrial membrane potential, reactive oxygen species (ROS) generation, cytochrome c release, and subsequent induction of pro-caspase-9 and -3 processing. Cleavages of poly(ADP-ribose) polymerase (PARP) and DNA fragmentation factor (DFF-45) were accompanied by activation of caspase-9 and -3 triggered by shikonin in COLO 205 cells. Here, we found that shikonin-induced apoptotic cell death was accompanied by upregulation of p27, p53, and Bad and down-regulation of Bcl-2 and Bcl-XL, while shikonin had little effect on the levels of Bax protein. Taken together, we suggested that shikonin-induced apoptosis is triggered by the release of cytochrome c into cytosol, procaspase-9 processing, activation of caspase-3, degradation of PARP, and DNA fragmentation caused by the caspase-activated deoxyribonuclease through the digestion of DFF-45. The induction of apoptosis by shikonin may provide a pivotal mechanism for its cancer chemopreventive action. |
URI: | http://www.scopus.com/inward/record.url?eid=2-s2.0-4744374011&partnerID=MN8TOARS http://scholars.lib.ntu.edu.tw/handle/123456789/307470 |
DOI: | 10.1021/jf0495993 | SDG/Keyword: | caspase; cytochrome c; deoxyribonuclease; DNA; DNA fragment; dna fragmentation factor 45; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase; procaspase 3; procaspase 9; protein BAD; protein Bax; protein bcl 2; protein bcl xl; protein p27; protein p53; reactive oxygen metabolite; shikonin; unclassified drug; antineoplastic activity; apoptosis; article; carcinoma cell; cell strain HL 60; colorectal carcinoma; controlled study; cytosol; human; human cell; IC 50; Lithospermum; lithospermum erythrorhizon; membrane potential; mitochondrial membrane; plant root; Anti-Inflammatory Agents, Non-Steroidal; Apoptosis; Caspase 3; Caspase 9; Caspases; Cell Cycle Proteins; Colorectal Neoplasms; Cyclin-Dependent Kinase Inhibitor p27; Cytochromes c; DNA Fragmentation; Enzyme Activation; Humans; Membrane Potentials; Mitochondria; Naphthoquinones; Poly(ADP-ribose) Polymerases; Proteins; Proto-Oncogene Proteins c-bcl-2; Reactive Oxygen Species; Tumor Cells, Cultured; Tumor Suppressor Protein p53; Tumor Suppressor Proteins; Lithospermum; Lithospermum erythrorhizon |
Appears in Collections: | 食品科技研究所 |
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