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. 2008 Nov;9(11):2265-2277.
doi: 10.3390/ijms9112265. Epub 2008 Nov 19.

Ponicidin inhibits monocytic leukemia cell growth by induction of apoptosis

Jia-Jun Liu  1 , Yong Zhang  2 , Wei-Bin Guang  3 , Hong-Zhi Yang  3 , Dong-Jun Lin  1 , Ruo-Zhi Xiao  1
Affiliations

Ponicidin inhibits monocytic leukemia cell growth by induction of apoptosis

Jia-Jun Liu et al. Int J Mol Sci. 2008 Nov.

Abstract

In this study two monocytic leukemia cell lines, U937 and THP-1 cells, were used to investigate the anti-proliferation effects caused by ponicidin. Cell viability was measured by an MTT assay. Cell apoptosis was assessed by flow cytometry as well as DNA fragmentation analysis. Cell morphology was observed using an inverted microscope and Hoechst 33258 staining. RT-PCR and Western blot analysis were used to detect survivin as well as Bax and Bcl-2 expressions after the cells were treated with different concentrations of ponicidin. The results revealed that ponicidin could inhibit the growth of U937 and THP-1 cells significantly by induction of apoptosis. The suppression was in both time- and dose-dependent manner. Marked morphological changes of cell apoptosis were observed clearly after the cells were treated with ponicidin for 48 approximately 72 h. RT-PCR and Western blot analysis demonstrated that both survivin and Bcl-2 expressions were down-regulated remarkably while Bax expression remained constant before and after apoptosis occurred. We therefore conclude that ponicidin has significant anti-proliferation effects by inducing apoptosis on leukemia cells in vitro, downregulation of survivin as well as Bcl-2 expressions may be the important apoptosis inducing mechanisms. The results suggest that ponicidin may serve as potential therapeutic agent for leukemia.

Keywords: Bax; Bcl-2; Leukemia; Ponicidin; Survivin.

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Figures

Figure 1.
Figure 1.
Cell viability caused by ponicidin.
Figure 2.
Figure 2.
Cell apoptosis caused by ponicidin.
Figure 3.
Figure 3.
Flow histogram of sub-G1 cells.
Figure 4.
Figure 4.
Expression of pro-and anti-apoptotic genes detected by RT-PCR and Western blot. Expression of pro-and anti-apoptotic genes was detected by RT-PCR (A) and Western blot (B) after treatment with 40 μmol/L ponicidin for 48 and 72 h. Both mRNA and protein levels of Survivin and Bcl-2 were down-regulated while the mRNA expression and protein level of Bax remained constant.
Figure 5.
Figure 5.
Apoptosis observed by Hoechst 33258 staining (200×). After the cells were treated with 40 μmol/L ponicidin, Hoechst 33258 staining was used to observe the morphological changes of cell apoptosis. Morphological changes of cell apoptosis such as condensation of chromatin and nuclear fragmentations were found clearly. A: Control; B: Cells treated for 48 h; C:Cells treated for 72 h. 1. U937; 2. THP-1.
Figure 6.
Figure 6.
DNA fragmentation analysis.
See this image and copyright information in PMC

References

    1. Han QB, Li ML, Li SH, Mou YK, Lin ZW, Sun HD. Ent-kaurane diterpenoids from Isodon rubescens var. lushanensis. Chem. Pharm. Bull. 2003;51:790–793. - PubMed
    1. Zhang JX, Han QB, Zhao AH, Sun HD. Diterpenoids from Isodon japonica. Fitoterapia. 2003;74:435–438. - PubMed
    1. Osawa K, Yasuda H, Maruyama T, Morita H, Takeya K, Itokawa H. Antibactirial trichorabdal diterpenes from Rabdosia trichocarpa. Phytochemistry. 1994;36:1287–1291. - PubMed
    1. Li SH, Niu XM, Peng LY, Zhang HJ, Yao P, Sun HD. Ent-Kaurane diterpenoids from the leaves of Isodon xerophilus. Planta. Med. 2002;68:946–948. - PubMed
    1. Hayashi K, Hayashi T, Sun HD, Takeda Y. Contribution of a combination of ponicidin and acyclovir/ganciclovir to the antitumor efficacy of the herpes simplex virus thymidine kinase gene therapy system. Hum. Gene Ther. 2002;13:415–423. - PubMed