Targeted RNA interference of cyclin A2 mediated by functionalized single-walled carbon nanotubes induces proliferation arrest and apoptosis in chronic myelogenous leukemia K562 cells.
Cyclin A(2) plays critical role in DNA replication, transcription, and cell cycle regulation. Its overexpression has been detected and related to many types of cancers including leukemia, suggesting that suppression of cyclin A(2) would be an attractive strategy to prevent tumor progression. Herein, we apply functionalized single wall carbon nanotubes (f-SWNTs) to carry small interfering RNA (siRNA) into K562 cells and determine whether inhibition of cyclin A(2) would be a potential therapeutic target for chronic myelogenous leukemia. The results show functionalized SWNTs can facilitate the coupling of siRNA specifically targeting human cyclin A(2) to form cyclin A(2) siRNA-f-SWNTs complexes. These functionalized SWNTs readily enter K562 cells, resulting in suppression of cyclin A(2) expression. We demonstrate that depletion of cyclin A(2) in this manner inhibits cell proliferation and promotes apoptosis, and cyclin A(2) can serve as a novel therapeutic target. siRNA against cyclin A(2) delivered by functionalized single wall carbon nanotubes may be a useful therapeutic strategy for chronic myelogenous leukemia cells. This would provide new insights on additional therapeutic options for chronic myelogenous leukemia beyond chemotherapy in light of increasing multidrug resistance.
Wang
Xiaohui
X
Division of Biological Inorganic Chemistry, Key Laboratory of Rare Earth Chemistry and Physics, Graduate School of the Chinese Academy of Sciences, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, China.
Ren
Jinsong
J
Qu
Xiaogang
X
D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D019925:Cyclin A / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D056751:Cyclin A2; D004337:Drug Carriers / Q000737:chemistry; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000378:metabolism; D037742:Nanotubes, Carbon / Q000737:chemistry*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*
D000970:Antineoplastic Agents; C503721:CCNA2 protein, human; D019925:Cyclin A; D056751:Cyclin A2; D004337:Drug Carriers; D037742:Nanotubes, Carbon; D034741:RNA, Small Interfering