Tetrathiomolybdate sensitizes ovarian cancer cells to anticancer drugs doxorubicin, fenretinide, 5-fluorouracil and mitomycin C.
Kyu Kwang Kim, Thilo S Lange, Rakesh K Singh, Laurent Brard, Richard G Moore
Index: BMC Cancer 12 , 147, (2012)
Full Text: HTML
Abstract
Our recent study showed that tetrathiomolybdate (TM), a drug to treat copper overload disorders, can sensitize drug-resistant endometrial cancer cells to reactive oxygen species (ROS)-generating anticancer drug doxorubicin. To expand these findings in the present study we explore TM efficacy in combination with a spectrum of ROS-generating anticancer drugs including mitomycin C, fenretinide, 5-fluorouracil and doxorubicin in ovarian cancer cells as a model system.The effects of TM alone or in combination with doxorubicin, mitomycin C, fenretinide, or 5-fluorouracil were evaluated using a sulforhodamine B assay. Flow cytometry was used to detect the induction of apoptosis and ROS generation. Immunoblot analysis was carried out to investigate changes in signaling pathways.TM potentiated doxorubicin-induced cytotoxicity and modulated key regulators of apoptosis (PARP, caspases, JNK and p38 MAPK) in SKOV-3 and A2780 ovarian cancer cell lines. These effects were linked to the increased production of ROS, as shown in SKOV-3 cells. ROS scavenging by ascorbic acid blocked the sensitization of cells by TM. TM also sensitized SKOV-3 to mitomycin C, fenretinide, and 5-fluorouracil. The increased cytotoxicity of these drugs in combination with TM was correlated with the activity of ROS, loss of a pro-survival factor (e.g. XIAP) and the appearance of a pro-apoptotic marker (e.g. PARP cleavage).Our data show that TM increases the efficacy of various anticancer drugs in ovarian cancer cells in a ROS-dependent manner.
Related Compounds
Related Articles:
2015-03-17
[Anal. Chem. 87(6) , 3388-95, (2015)]
Potentiation of antibiofilm activity of amphotericin B by superoxide dismutase inhibition.
2013-01-01
[Oxid. Med. Cell. Longev. 2013 , 704654, (2013)]
2007-03-16
[J. Org. Chem. 72 , 2106, (2007)]
Copper lowering therapy with tetrathiomolybdate as an antiangiogenic strategy in cancer.
2005-05-01
[Curr. Cancer Drug Targets 5 , 195, (2005)]
Flower-like PEGylated MoS2 nanoflakes for near-infrared photothermal cancer therapy.
2015-01-01
[Sci. Rep. 5 , 17422, (2015)]