当前位置： SCI文献检索 > ANTICANCER RESEARCH期刊下所有文献 > Biological evaluation of 2,3-dichloro-5,8-dimethoxy-1,4-naphthoquinone as an anti-breast cancer agent.

Biological evaluation of 2,3-dichloro-5,8-dimethoxy-1,4-naphthoquinone as an anti-breast cancer agent.

Abstract：

BACKGROUND:Breast cancer is the most frequent cancer and the second leading cause of cancer deaths in women today. A number of 1,4-naphthoquinone derivatives have been found to possess significant pharmacological effects associated with marked antimicrobial and antitumor activities. In the present study, the in vitro effect of 2,3-dichloro-5,8-dimethoxy-1,4-naphthoquinone (DCDMNQ) was evaluated on estrogen-positive MCF-7 and estrogen-negative MDA-MB-436 and Hs-578T human breast cancer cell lines. Moreover, the in vitro activity of this compound on cell cycle regulation and apoptosis were evaluated. MATERIALS AND METHODS:Established methods of cell viability, cell cycle, Western blot and apoptosis were used. RESULTS:The effect of DCDMNQ on MCF-7, MDA-MB-436 and Hs-578T cells revealed significant antitumor activities with IC(50)s, of 0.6 +/- 0.02, 1.4 +/- 0.25 and 3.1 +/- 0.4 microM respectively. Cell cycle analysis showed that DCDMNQ inhibited progression through the cell cycle in MCF-7 and MDA-MB-436 cell lines in a time-dependent manner. DCDMNQ arrested cells in the S-phase of the cell cycle with the greatest proportion of cells in the S-phase by day 5. This cell-cycle arrest was corroborated by inhibition of topoisomerase I induced by DCDMNQ. These findings were further validated using Western blot analysis of retinoblastoma protein time-dependent phosphorylation. Furthermore, DCDMNQ induced apoptosis in both estrogen-positive and -negative cell lines in a time-dependent manner. However, the highest percentages of apoptotic cells were observed in the MDA-MB-436 cell line. CONCLUSION:Although the mechanism of action of DCDMNQ has not been completely elucidated, it appears that this compound can inhibit topoisomerase I in a concentration-dependent manner. These promising results to explore novel naphthoquinone analogues as potential breast cancer agents. This study suggests that DCDMNQ may have an impact on treatment of estrogen-positive and -negative breast cancer while protecting the bone marrow.

journal_name

Anticancer Res

journal_title

Anticancer research

authors

Kanaan YM,Das JR,Bakare O,Enwerem NM,Berhe S,Beyene D,Williams V,Zhou Y,Copeland RL Jr

subject

Has Abstract

pub_date

2009-01-01 00:00:00

pages

191-9

issue

1

eissn

0250-7005

issn

1791-7530

journal_volume

29

pub_type

杂志文章

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