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

Journal of Autacoids and Hormones

Author(s): Kanaan YM, Das JR, Bakare O, Enwerem NM, Berhe S,

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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.
This article was published in Anticancer Res and referenced in Journal of Autacoids and Hormones

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