DMU-212 inhibits tumor growth in xenograft model of human ovarian cancer.
DMU-212 has been shown to evoke a mitochondrial apoptotic pathway in transformed fibroblasts and breast cancer. However, recently published data indicated the ability of DMU-212 to evoke apoptosis in both mitochondria- and receptor-mediated manner in two ovarian cancer cell lines, namely A-2780 and SKOV-3, which showed varied sensitivity to the compound tested. The pronounced cytotoxic effects of DMU-212 observed in A-2780 cells were related to the execution of extracellular apoptosis pathway and cell cycle arrest in G2/M phase. In view of the great anticancer potential of DMU-212 against A-2780 cell line, the aim of the current study was to assess antiproliferative activity of DMU-212 in xenograft model of ovarian cancer. To evaluate in vitro metabolic properties of cells that were to be injected into SCID mice, uptake and decline of DMU-212 in A-2780 ovarian cancer cell line was investigated. It was found that the concentration of the test compound in A-2780 cells was growing within first eight hours, and then the gradual decline was observed. A-2780 cells stably transfected with pcDNA3.1/Zeo(-)-Luc vector were subcutaneously inoculated into the right flanks of SCID mice. After seven days of the treatment with DMU-212 (50mg/kg b.w), tumor growth appeared to be suppressed in the animals treated with the compound tested. At day 14 of the experiment, tumor burden in mice treated with DMU-212 was significantly lower, as compared to untreated controls. Our findings suggest that DMU-212 might be considered as a potential anticancer agent used in ovarian cancer therapy.
Department of Toxicology, Poznan University of Medical Sciences, Poznan, Poland. Electronic address: hanna.piotrowska@ump.edu.pl.
Hanna
H
Piotrowska
Department of Toxicology, Poznan University of Medical Sciences, Poznan, Poland. Electronic address: myszkowski.krzysztof.a@gmail.com.
Krzysztof
K
Myszkowski
Department of Toxicology, Poznan University of Medical Sciences, Poznan, Poland.
Joanna
J
Abraszek
Chair of Medical Biotechnology, Poznan University of Medical Sciences, Poznan, Poland; Department of Cancer Diagnostics and Immunology, Greater Poland Cancer Centre, Poznan, Poland. Electronic address: eliza.kwiatkowska@wco.pl.
Eliza
E
Kwiatkowska-Borowczyk
Institute of Animal Reproduction and Food Research of the Polish Academy of Sciences, Olsztyn, Poland. Electronic address: amaro@pan.olsztyn.pl.
Ryszard
R
Amarowicz
Department of Toxicology, Poznan University of Medical Sciences, Poznan, Poland. Electronic address: marek.murias@ump.edu.pl.
Marek
M
Murias
Department of Chemical Technology of Drugs, Poznan University of Medical Sciences, Poznan, Poland. Electronic address: mwierzch@ump.edu.pl.
Marcin
M
Wierzchowski
Department of Toxicology, Poznan University of Medical Sciences, Poznan, Poland. Electronic address: liebert@ump.edu.pl.
Jadwiga
J
Jodynis-Liebert
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D013267:Stilbenes / Q000494:pharmacology*; D013997:Time Factors; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
C482492:3,4,5,4'-tetramethoxystilbene; D000970:Antineoplastic Agents; D013267:Stilbenes
3,4,4′5-tetramethoxystilbene (DMU-212); Ovarian cancer; Xenograft model