Induction of G2/M phase arrest by squamocin in chronic myeloid leukemia (K562) cells.
Squamocin is one of the annonaceous acetogenins and has been reported to have anticancer activity. Squamocin was found to inhibit the growth of K562 cells in a time- and dose-dependent manner. Cell cycle analysis showed G2/M phase arrest in K562 cells following 24 h exposure to squamocin. During the G2/M arrest, cyclin-dependent kinase inhibitors (CDKIs), p21 and p27 were increased in a dose-dependent manner. Analysis of the cell cycle regulatory proteins demonstrated that squamocin did not change the steady-state levels of Cdk2, Cdk4, cyclin A, cyclin B1, cyclin D3 and cyclin E, but decreased the protein levels of Cdk1 and Cdc25C. These results suggest that squamocin inhibits the proliferation of K562 cells via G2/M arrest in association with the induction of p21, p27 and the reduction of Cdk1 and Cdc25C kinase activities.
Lu
Mei-Chin
MC
Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 807, Taiwan, ROC.
Yang
Sheng-Huei
SH
Hwang
Shiuh-Lin
SL
Lu
Yu-Jhang
YJ
Lin
Yi-Hsiung
YH
Wang
Sen-Ren
SR
Wu
Yang-Chang
YC
Lin
Shinne-Ren
SR
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D015153:Blotting, Western; D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology; D002455:Cell Division / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D005663:Furans / Q000494:pharmacology*; D016195:G2 Phase / Q000187:drug effects*; D016370:Gene Products, rex / Q000096:biosynthesis; D006801:Humans; D020014:K562 Cells; D007783:Lactones / Q000494:pharmacology*; D015689:Oncogene Protein p21(ras) / Q000096:biosynthesis; D020687:cdc25 Phosphatases / Q000037:antagonists & inhibitors / Q000096:biosynthesis
D000972:Antineoplastic Agents, Phytogenic; D018797:Cell Cycle Proteins; D005663:Furans; D016370:Gene Products, rex; D007783:Lactones; C059660:squamocin; D016203:CDC2 Protein Kinase; C517009:CDC25C protein, human; D020687:cdc25 Phosphatases; D015689:Oncogene Protein p21(ras)