The Cytotoxicity and Mechanisms of 1,2-naphthoquinone Thiosemicarbazone and Its Metal Derivatives against Mcf-7 Human Breast Cancer Cells


We have investigated the antitumor functions and mechanisms of 1,2-naphthoquinone-2-thiosemicarbazone (NQTS) and its metal complexes (Cu 2+, Pd2+, and Ni2+) against MCF-7 human breast cancer cells. The cells were dosed with these complexes at varying concentrations, and cell viability was measured by a sulforhodamine B (SRB) method. To study mechanisms of action, the complexes were incubated with topoisomerase II (topo II) and supercoiled DNA, linear DNA, nicked open DNA, and relaxed DNA were detected by agarose gel electrophoresis. The results revealed that these complexes are effective antitumor chemicals in inhibiting MCF-7 cell growth, with Ni-NQTS being the most effective among the complexes studied. Our data also indicated that Ni-NQTS is more effective than the commercial antitumor drug, etoposide, based on IC50 values. The mechanistic study of action showed that metal complexes of NQTS, NQ, and NQTS can only stabilize the single-strand nicked DNA, but not double-strand breakage intermediates. In addition, metal derivatives of these ligands, but not the parent NQ and NQTS, exerted an antagonizing effect on topoisomerase II activity. In summary, chemicals with or without metal derivatives might possess different chemical-topoisomerase II-DNA interactions.


Biological Sciences

Second Department


Keywords and Phrases

1,2 naphthoquinone thiosemicarbazone; etoposide; thiosemicarbazone derivative; unclassified drug; antineoplastic activity; breast cancer; cancer cell; cell viability; complex formation; controlled study; cytotoxicity; drug mechanism; enzyme activity; human; human cell; IC 50; ligand binding; Antineoplastic Agents; Apoptosis; Breast Neoplasms; Cell Line, Tumor; DNA Topoisomerases, Type II; DNA, Neoplasm; Dose-Response Relationship, Drug; Female; Humans; In Situ Nick-End Labeling; Indicators and Reagents; Metals; Naphthoquinones; Mink cell focus-forming virus

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Article - Journal

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© 2004 Elsevier, All rights reserved.

Publication Date

15 May 2004