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. 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.
State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China. fengqianmoon@163.com.
Qian
Q
Feng
State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China. michael_jackydog@hotmail.com.
Wa Seng
WS
Leong
State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China. lliu@must.edu.mo.
Liang
L
Liu
State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China. pollychan8375@gmail.com.
Wai-In
WI
Chan
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002298:Cardenolides / Q000494:pharmacology*; D002301:Cardiac Glycosides / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004074:Digitoxin / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020014:K562 Cells; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D010042:Ouabain / Q000494:pharmacology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism
D000970:Antineoplastic Agents; C493956:CDKN1A protein, human; D002298:Cardenolides; D002301:Cardiac Glycosides; D050759:Cyclin-Dependent Kinase Inhibitor p21; D010042:Ouabain; C100098:cannogenin thevetoside; D004074:Digitoxin; D011065:Poly(ADP-ribose) Polymerases; C505407:CASP3 protein, human; C505530:CASP8 protein, human; D053148:Caspase 3; D053181:Caspase 8
Peruvoside; acute myeloid leukemia; cardiac glycoside