Peruvoside, a Cardiac Glycoside, Induces Primitive Myeloid Leukemia Cell Death
Despite the available chemotherapy and treatment, leukemia remains a difficult disease to cure due to frequent relapses after treatment. Among the heterogeneous leukemic cells, a rare population referred as the leukemic stem cell (LSC), is thought to be responsible for relapses and drug resistance....
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MDPI AG
2016-04-01
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| Series: | Molecules |
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| Online Access: | http://www.mdpi.com/1420-3049/21/4/534 |
| _version_ | 1811194113695940608 |
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| author | Qian Feng Wa Seng Leong Liang Liu Wai-In Chan |
| author_facet | Qian Feng Wa Seng Leong Liang Liu Wai-In Chan |
| author_sort | Qian Feng |
| collection | DOAJ |
| description | Despite the available chemotherapy and treatment, leukemia remains a difficult disease to cure due to frequent relapses after treatment. Among the heterogeneous leukemic cells, a rare population referred as the leukemic stem cell (LSC), is thought to be responsible for relapses and drug resistance. Cardiac glycosides (CGs) have been used in treating heart failure despite its toxicity. Recently, increasing evidence has demonstrated its new usage as a potential anti-cancer drug. Ouabain, one of the CGs, specifically targeted CD34+CD38− leukemic stem-like cells, but not the more mature CD34+CD38+ leukemic cells, making this type of compounds a potential treatment for leukemia. In search of other potential anti-leukemia CGs, we found that Peruvoside, a less studied CG, is more effective than Ouabain and Digitoxin at inducing cell death in primitive myeloid leukemia cells without obvious cytotoxicity on normal blood cells. Similar to Ouabain and Digitoxin, Peruvoside also caused cell cycle arrest at G2/M stage. It up-regulates CDKN1A expression and activated the cleavage of Caspase 3, 8 and PARP, resulting in apoptosis. Thus, Peruvoside showed potent anti-leukemia effect, which may serve as a new anti-leukemia agent in the future. |
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| id | doaj.art-c293e4c03ed34fb48d4c7d3f56b265e9 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-04-12T00:20:33Z |
| publishDate | 2016-04-01 |
| publisher | MDPI AG |
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| series | Molecules |
| spelling | doaj.art-c293e4c03ed34fb48d4c7d3f56b265e92022-12-22T03:55:44ZengMDPI AGMolecules1420-30492016-04-0121453410.3390/molecules21040534molecules21040534Peruvoside, a Cardiac Glycoside, Induces Primitive Myeloid Leukemia Cell DeathQian Feng0Wa Seng Leong1Liang Liu2Wai-In Chan3State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, ChinaState Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, ChinaState Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, ChinaState Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, ChinaDespite the available chemotherapy and treatment, leukemia remains a difficult disease to cure due to frequent relapses after treatment. Among the heterogeneous leukemic cells, a rare population referred as the leukemic stem cell (LSC), is thought to be responsible for relapses and drug resistance. Cardiac glycosides (CGs) have been used in treating heart failure despite its toxicity. Recently, increasing evidence has demonstrated its new usage as a potential anti-cancer drug. Ouabain, one of the CGs, specifically targeted CD34+CD38− leukemic stem-like cells, but not the more mature CD34+CD38+ leukemic cells, making this type of compounds a potential treatment for leukemia. In search of other potential anti-leukemia CGs, we found that Peruvoside, a less studied CG, is more effective than Ouabain and Digitoxin at inducing cell death in primitive myeloid leukemia cells without obvious cytotoxicity on normal blood cells. Similar to Ouabain and Digitoxin, Peruvoside also caused cell cycle arrest at G2/M stage. It up-regulates CDKN1A expression and activated the cleavage of Caspase 3, 8 and PARP, resulting in apoptosis. Thus, Peruvoside showed potent anti-leukemia effect, which may serve as a new anti-leukemia agent in the future.http://www.mdpi.com/1420-3049/21/4/534cardiac glycosidePeruvosideacute myeloid leukemia |
| spellingShingle | Qian Feng Wa Seng Leong Liang Liu Wai-In Chan Peruvoside, a Cardiac Glycoside, Induces Primitive Myeloid Leukemia Cell Death Molecules cardiac glycoside Peruvoside acute myeloid leukemia |
| title | Peruvoside, a Cardiac Glycoside, Induces Primitive Myeloid Leukemia Cell Death |
| title_full | Peruvoside, a Cardiac Glycoside, Induces Primitive Myeloid Leukemia Cell Death |
| title_fullStr | Peruvoside, a Cardiac Glycoside, Induces Primitive Myeloid Leukemia Cell Death |
| title_full_unstemmed | Peruvoside, a Cardiac Glycoside, Induces Primitive Myeloid Leukemia Cell Death |
| title_short | Peruvoside, a Cardiac Glycoside, Induces Primitive Myeloid Leukemia Cell Death |
| title_sort | peruvoside a cardiac glycoside induces primitive myeloid leukemia cell death |
| topic | cardiac glycoside Peruvoside acute myeloid leukemia |
| url | http://www.mdpi.com/1420-3049/21/4/534 |
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