Cytotoxic and apoptotic effects of prenylflavonoid artonin B in human acute lymphoblastic leukemia cells.

Acta Pharmacol Sin 2006 Sep;27(9):1165-74

Department of Medical Education and Research, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan China.

Aim: To investigate the anticancer effects and molecular mechanism of artonin B on the human acute lymphoblastic leukemia CCRF-CEM cells compared with other prenylflavonoid compounds.

Methods: The effects of four prenylflavonoids on the growth of CCRF-CEM and HaCa cells were studied by 3-(4,5)-2,5-diphenyl-tetrazolium bromide (MTT) assay. Apoptosis were detected through Hoechst 33258 staining. The effect of artonin B on the cell cycle of CCRF-CEM cells were studied by propidium iodide method. The change in mitochondrial membrane potential was detected by rohdamine 123 staining. The cytochrome c release and caspase 3 activity were checked by immunoassay kits, respectively. The expression of Bcl-2 family proteins was detected by Western blot.

Results: Our data revealed that artonin B strongly induced human CCRF-CEM leukemia cell death in a dose- and time-dependent manner by MTT assay, but not on normal epithelia cells (HaCa cells). Artonin B-induced cell death was considered to be apoptotic by observing the typical apoptotic morphological change by Hoechst 33258 staining. The induction of human CCRF-CEM leukemia cancer cell death was caused by an induction of apoptosis through mitochondrial membrane potential change, cytochrome c release, sub-G1 proportion increase, downregulation of Bcl-2 expression, upregulation of Bax and Bak expression and activation of caspase 3 pathways.

Conclusion: These results clearly demonstrated that artonin B is able to inhibit proliferation by induction of hypoploid cells and cell apoptosis. Moreover, the anticancer effects of artonin B were related to mitochondrial pathway and caspase 3 activation in human CCRF-CEM leukemia cells.

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http://dx.doi.org/10.1111/j.1745-7254.2006.00404.xDOI Listing
September 2006
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References

(Supplied by CrossRef)

Gao Z et al.
Biochim Biophys Acta 1999

Larocca LM et al.
J Urol 1994

Komori A et al.
Jpn J Clin Oncol 1993

Ren S et al.
Prog Drug Res 1997

Hano Y et al.
Heterocycles 1989

Wyllie AH. et al.
Br J Cancer 1993

Thompson CB. et al.
Science 1995

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