Aurora-A kinase inhibition enhances the cytosine arabinoside-induced cell death in leukemia cells through apoptosis and mitotic catastrophe.
Aurora-A (Aur-A) is a centrosome-associated serine/threonine kinase that is overexpressed in various cancers and potentially correlated with chemoresistance. In the Ara-C-sensitive leukemia cell lines, silencing of Aur-A by small interfering RNA transfection led to a significant increase in the Ara-C-induced cell death rate through induction of mitochondria-mediated, caspase-dependent apoptosis. In contrast, combined treatment of the Ara-C-resistant leukemia cell lines with Aur-A siRNA and Ara-C remarkably enhanced the cell death rate via non-caspase-dependent mitotic catastrophe. Taken together, Aur-A inhibition was an effective treatment for both the Ara-C-sensitive and resistant leukemia cells by increasing apoptosis and mitotic catastrophe, respectively.
Cheong
June-Won
JW
Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
Jung
Haeng-Im
HI
Eom
Ju In
JI
Kim
Soo Jung
SJ
Jeung
Hoi-Kyung
HK
Min
Yoo Hong
YH
D017209:Apoptosis / Q000187:drug effects; D064127:Aurora Kinases; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival; D003561:Cytarabine / Q000494:pharmacology*; D018922:HL-60 Cells; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology / Q000628:therapy*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D008938:Mitosis / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D014162:Transfection; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D034741:RNA, Small Interfering; D003561:Cytarabine; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020169:Caspases