Curcumin induces high levels of topoisomerase I- and II-DNA complexes in K562 leukemia cells.
Recent data suggest that curcumin, a phytochemical with cancer chemopreventive potential, might be useful in the treatment of several solid and hematological malignancies. DNA topoisomerases (topos) are the target of several drugs commonly used in cancer chemotherapy. These drugs induce topo-DNA complexes with either topo I or topo II; then cellular processing converts these complexes into permanent DNA strand breaks that trigger cell death. Using the TARDIS in vivo assay, this study shows for the first time that curcumin induces topo I and topo II (alpha and beta)-DNA complexes in K562 leukemia cells. A comparative analysis revealed that the levels of these complexes were higher than those induced by several standard topo I and topo II inhibitors at equitoxic doses. Curcumin-induced topo I and topo II-DNA complexes were prevented by the antioxidant N-acetylcysteine; this suggests that, unlike the standard topo inhibitors, reactive oxygen species may mediate the formation of these complexes. Overall, this work shows that curcumin is capable of inducing topo-DNA complexes in cells with both topo I and topo II and increases the evidence suggesting that this dietary agent has potential to be tested in cancer chemotherapy.
López-Lázaro
Miguel
M
Institute for Cell and Molecular Biosciences, The Medical School, Newcastle University, Newcastle-upon-Tyne, UK.
Willmore
Elaine
E
Jobson
Andrew
A
Gilroy
Kathryn L
KL
Curtis
Hannah
H
Padget
Kay
K
Austin
Caroline A
CA
D000111:Acetylcysteine / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D003474:Curcumin / Q000737:chemistry / Q000494:pharmacology*; D004247:DNA / Q000187:drug effects / Q000378:metabolism*; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020014:K562 Cells; D008856:Microscopy, Fluorescence; D015394:Molecular Structure; D017382:Reactive Oxygen Species / Q000494:pharmacology; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D000975:Antioxidants; D017382:Reactive Oxygen Species; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D004247:DNA; D004264:DNA Topoisomerases, Type I; D004250:DNA Topoisomerases, Type II; D003474:Curcumin; D000111:Acetylcysteine