Biological Evaluation of 2,3-Dichloro-5,8-Dimethoxy-1,4-Naphthoquinone as an Anti-breast Cancer Agent

• Published in: Anticancer research 2009-01, Vol.29 (1), p.191-199
• Main Authors: KANAAN, Yasmine M, DAS, Jharna R, BAKARE, Oladapo, ENWEREM, Nkechi M, BERHE, Solomon, BEYENE, Desta, WILLIAMS, Vonita, YANFEI ZHOU, COPELAND, Robert L
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - pharmacology; Apoptosis - drug effects; Biological and medical sciences; Blotting, Western; Breast Neoplasms - drug therapy; Breast Neoplasms - enzymology; Breast Neoplasms - metabolism; Cell Cycle - drug effects; Cell Line, Tumor; Cell Survival - drug effects; DNA Topoisomerases, Type I - metabolism; Flow Cytometry; Gynecology. Andrology. Obstetrics; Humans; Mammary gland diseases; Medical sciences; Naphthoquinones - pharmacology; Topoisomerase I Inhibitors; Tumors
• ISSN: 0250-7005; 1791-7530

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 μM 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.