TY - JOUR
T1 - The cytotoxicity and mechanisms of 1,2-naphthoquinone thiosemicarbazone and its metal derivatives against MCF-7 human breast cancer cells
AU - Chen, Junnan
AU - Huang, Yue Wern
AU - Liu, Guanshu
AU - Afrasiabi, Zahra
AU - Sinn, Ekkehard
AU - Padhye, Subhash
AU - Ma, Yinfa
N1 - Funding Information:
This work was financially supported by the startup funds from the University of Missouri-Rolla to Yinfa Ma, Yue-wern Huang, and Ekkehard Sinn, respectively.
PY - 2004/5/15
Y1 - 2004/5/15
N2 - 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.
AB - 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.
KW - Anticancer chemicals
KW - Cytotoxicity
KW - MCF-7 cells
KW - Metal derivatives of 1,2-naphthoquinone- 2-thiosemicarbazone
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U2 - 10.1016/j.taap.2004.02.004
DO - 10.1016/j.taap.2004.02.004
M3 - Article
C2 - 15126073
AN - SCOPUS:2342447940
SN - 0041-008X
VL - 197
SP - 40
EP - 48
JO - Toxicology and Applied Pharmacology
JF - Toxicology and Applied Pharmacology
IS - 1
ER -