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

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.
Established methods of cell viability, cell cycle, Western blot and apoptosis were used.
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.
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.
AuthorsYasmine M Kanaan, Jharna R Das, Oladapo Bakare, Nkechi M Enwerem, Solomon Berhe, Desta Beyene, Vonita Williams, Yanfei Zhou, Robert L Copeland Jr
JournalAnticancer research (Anticancer Res) Vol. 29 Issue 1 Pg. 191-9 (Jan 2009) ISSN: 0250-7005 [Print] Greece
PMID19331150 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • 2,3-dichloro-5,8-dimethoxy-1,4-naphthoquinone
  • Antineoplastic Agents
  • Naphthoquinones
  • Topoisomerase I Inhibitors
  • DNA Topoisomerases, Type I
  • Antineoplastic Agents (pharmacology)
  • Apoptosis (drug effects)
  • Blotting, Western
  • Breast Neoplasms (drug therapy, enzymology, metabolism)
  • Cell Cycle (drug effects)
  • Cell Line, Tumor
  • Cell Survival (drug effects)
  • DNA Topoisomerases, Type I (metabolism)
  • Flow Cytometry
  • Humans
  • Naphthoquinones (pharmacology)
  • Topoisomerase I Inhibitors

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!

Choose Username:
Verify Password: