Compound K, a metabolite of ginseng saponin, induces apoptosis via caspase-8-dependent pathway in HL-60 human leukemia cells
<p>Abstract</p> <p>Background</p> <p>Compound K [20-<it>O</it>-β-(D-glucopyranosyl)-20(S)-protopanaxadiol], a metabolite of the protopanaxadiol-type saponins of <it>Panax ginseng </it>C.A. Meyer, has been reported to possess anti-tumor properties...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2009-12-01
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| Series: | BMC Cancer |
| Online Access: | http://www.biomedcentral.com/1471-2407/9/449 |
| _version_ | 1818759228758687744 |
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| author | Choi Jung-Hye Chung Kyung-Sook Cho Sung-Hee Kim Dong-Hyun Lee Kyung-Tae |
| author_facet | Choi Jung-Hye Chung Kyung-Sook Cho Sung-Hee Kim Dong-Hyun Lee Kyung-Tae |
| author_sort | Choi Jung-Hye |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Compound K [20-<it>O</it>-β-(D-glucopyranosyl)-20(S)-protopanaxadiol], a metabolite of the protopanaxadiol-type saponins of <it>Panax ginseng </it>C.A. Meyer, has been reported to possess anti-tumor properties to inhibit angiogenesis and to induce tumor apoptosis. In the present study, we investigated the effect of Compound K on apoptosis and explored the underlying mechanisms involved in HL-60 human leukemia cells.</p> <p>Methods</p> <p>We examined the effect of Compound K on the viabilities of various cancer cell lines using MTT assays. DAPI assay, Annexin V and PI double staining, Western blot assay and immunoprecipitation were used to determine the effect of Compound K on the induction of apoptosis.</p> <p>Results</p> <p>Compound K was found to inhibit the viability of HL-60 cells in a dose- and time-dependent manner with an IC<sub>50 </sub>of 14 μM. Moreover, this cell death had typical features of apoptosis, that is, DNA fragmentation, DNA ladder formation, and the externalization of Annexin V targeted phosphatidylserine residues in HL-60 cells. In addition, compound-K induced a series of intracellular events associated with both the mitochondrial- and death receptor-dependent apoptotic pathways, namely, (1) the activation of caspases-3, -8, and -9; (2) the loss of mitochondrial membrane potential; (3) the release of cytochrome <it>c </it>and Smac/DIABLO to the cytosol; (4) the translocation of Bid and Bax to mitochondria; and (5) the downregulations of Bcl-2 and Bcl-xL. Furthermore, a caspase-8 inhibitor completely abolished caspase-3 activation, Bid cleavage, and subsequent DNA fragmentation by Compound K. Interestingly, the activation of caspase-3 and -8 and DNA fragmentation were significantly prevented in the presence of cycloheximide, suggesting that Compound K-induced apoptosis is dependent on <it>de novo </it>protein synthesis.</p> <p>Conclusions</p> <p>The results indicate that caspase-8 plays a key role in Compound K-stimulated apoptosis via the activation of caspase-3 directly or indirectly through Bid cleavage, cytochrome <it>c </it>release, and caspase-9 activation.</p> |
| first_indexed | 2024-12-18T06:39:24Z |
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| publishDate | 2009-12-01 |
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| spelling | doaj.art-0dcc5439131c4b4c9e10426b9b3adfdf2022-12-21T21:17:41ZengBMCBMC Cancer1471-24072009-12-019144910.1186/1471-2407-9-449Compound K, a metabolite of ginseng saponin, induces apoptosis via caspase-8-dependent pathway in HL-60 human leukemia cellsChoi Jung-HyeChung Kyung-SookCho Sung-HeeKim Dong-HyunLee Kyung-Tae<p>Abstract</p> <p>Background</p> <p>Compound K [20-<it>O</it>-β-(D-glucopyranosyl)-20(S)-protopanaxadiol], a metabolite of the protopanaxadiol-type saponins of <it>Panax ginseng </it>C.A. Meyer, has been reported to possess anti-tumor properties to inhibit angiogenesis and to induce tumor apoptosis. In the present study, we investigated the effect of Compound K on apoptosis and explored the underlying mechanisms involved in HL-60 human leukemia cells.</p> <p>Methods</p> <p>We examined the effect of Compound K on the viabilities of various cancer cell lines using MTT assays. DAPI assay, Annexin V and PI double staining, Western blot assay and immunoprecipitation were used to determine the effect of Compound K on the induction of apoptosis.</p> <p>Results</p> <p>Compound K was found to inhibit the viability of HL-60 cells in a dose- and time-dependent manner with an IC<sub>50 </sub>of 14 μM. Moreover, this cell death had typical features of apoptosis, that is, DNA fragmentation, DNA ladder formation, and the externalization of Annexin V targeted phosphatidylserine residues in HL-60 cells. In addition, compound-K induced a series of intracellular events associated with both the mitochondrial- and death receptor-dependent apoptotic pathways, namely, (1) the activation of caspases-3, -8, and -9; (2) the loss of mitochondrial membrane potential; (3) the release of cytochrome <it>c </it>and Smac/DIABLO to the cytosol; (4) the translocation of Bid and Bax to mitochondria; and (5) the downregulations of Bcl-2 and Bcl-xL. Furthermore, a caspase-8 inhibitor completely abolished caspase-3 activation, Bid cleavage, and subsequent DNA fragmentation by Compound K. Interestingly, the activation of caspase-3 and -8 and DNA fragmentation were significantly prevented in the presence of cycloheximide, suggesting that Compound K-induced apoptosis is dependent on <it>de novo </it>protein synthesis.</p> <p>Conclusions</p> <p>The results indicate that caspase-8 plays a key role in Compound K-stimulated apoptosis via the activation of caspase-3 directly or indirectly through Bid cleavage, cytochrome <it>c </it>release, and caspase-9 activation.</p>http://www.biomedcentral.com/1471-2407/9/449 |
| spellingShingle | Choi Jung-Hye Chung Kyung-Sook Cho Sung-Hee Kim Dong-Hyun Lee Kyung-Tae Compound K, a metabolite of ginseng saponin, induces apoptosis via caspase-8-dependent pathway in HL-60 human leukemia cells BMC Cancer |
| title | Compound K, a metabolite of ginseng saponin, induces apoptosis via caspase-8-dependent pathway in HL-60 human leukemia cells |
| title_full | Compound K, a metabolite of ginseng saponin, induces apoptosis via caspase-8-dependent pathway in HL-60 human leukemia cells |
| title_fullStr | Compound K, a metabolite of ginseng saponin, induces apoptosis via caspase-8-dependent pathway in HL-60 human leukemia cells |
| title_full_unstemmed | Compound K, a metabolite of ginseng saponin, induces apoptosis via caspase-8-dependent pathway in HL-60 human leukemia cells |
| title_short | Compound K, a metabolite of ginseng saponin, induces apoptosis via caspase-8-dependent pathway in HL-60 human leukemia cells |
| title_sort | compound k a metabolite of ginseng saponin induces apoptosis via caspase 8 dependent pathway in hl 60 human leukemia cells |
| url | http://www.biomedcentral.com/1471-2407/9/449 |
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