Induction of G2/M phase arrest and apoptosis by a novel enediyne derivative, THDA, in chronic myeloid leukemia (K562) cells.
We studied the effect of 2-(6-(2-thieanisyl)-3(Z)-hexen-1,5-diynyl)aniline(THDA), a newly developed anti-cancer agent, on cell proliferation, cell cycle progression, and induction of apoptosis in K562 cells. THDA was found to inhibit the growth of K562 cells in a time-and dose-dependent manner. Cell cycle analysis showed G2/M phase arrest and apoptosis in K562 cells following 24 h exposure to THDA. During the G2/M arrest, cyclin-dependent kinase inhibitors (CDKIs), p21 and p27 were increased in a time-dependent manner. Analysis of the cell cycle regulatory proteins demonstrated that THDA did not change the steady-state levels of cyclin B1, cyclin D3 and Cdc25C, but decreased the protein levels of Cdk1, Cdk2 and cyclin A. THDA also caused a marked increase in apoptosis, which was associated with activation of caspase-3 and proteolytic cleavage of poly (ADP-ribose) polymerase. These molecular alterations provide an insight into THDA-caused growth inhibition, G2/M arrest and apoptotic death of K562 cells.
Wu
Zchong-Zcho
ZZ
Faculty of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung 807, Taiwan, ROC.
Chien
Ching-Ming
CM
Yang
Sheng-Huei
SH
Lin
Yi-Hsiung
YH
Hu
Xiu-Wei
XW
Lu
Yu-Jhang
YJ
Wu
Ming-Jung
MJ
Lin
Shinne-Ren
SR
D000814:Aniline Compounds / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D053281:Enediynes / Q000737:chemistry / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D016195:G2 Phase / Q000187:drug effects*; D006801:Humans; D015151:Immunoblotting; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000473:pathology*; D008214:Lymphocytes / Q000187:drug effects; D008938:Mitosis / Q000187:drug effects*
C516307:2-(6-(2-thieanisyl)-3-hexen-1,5-diynyl)aniline; D000814:Aniline Compounds; D053281:Enediynes; D053148:Caspase 3