Possible protective effects of alpha-tocopherol on enhanced induction of reactive oxygen species by 2-methoxyestradiol in tumors.
Several non-surgical tumor treatment modalities produce their cytotoxic activity by generating reactive oxygen species (ROS). Anti-oxidative enzymes such as superoxide dismutase (SOD) or exogenously supplied antioxidants may therefore reduce the efficacy of these treatments. The aim of the present study was to analyze the impact of (i) inhibiting SOD using 2-methoxyestradiol (2-ME), or (ii) application of alpha-tocopherol, on the cellular damage induced by hyperthermia (HT) in experimental tumors. DS-sarcoma cells grew either in culture or as solid tumors subcutaneously implanted in rats. In vitro, DS-cells were incubated with 2-ME, and cell proliferation, ROS formation, lipid peroxidation and apoptosis were measured. In vivo, DS-sarcomas were treated with a ROS-generating hyperthermia combined with 2-ME or alpha-tocopherol application. Inhibition of SOD by 2-ME in vitro induced pronounced oxidative injury resulting in reduced proliferation. In vivo, ROS-generating hyperthermia led to local tumor control in 23% of the animals. The additional inhibition of SOD by 2-ME increased the control rate by approximately 50%. Application of alpha-tocopherol was found to have no effect on local tumor control, either in combination with ROS-generating hyperthermia or when 2-ME was additionally applied. Inhibition of SOD during ROS-generating hyperthermia results in pronounced cell injury and an improved local tumor control whereas exogenously applied vitamin E seems not to have an impact on oxidative stress.
Thews
Oliver
O
Lambert
Christine
C
Kelleher
Debra K
DK
Biesalski
Hans-Konrad
HK
Vaupel
Peter
P
Frank
Jürgen
J
D000077584:2-Methoxyestradiol; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012513:Sarcoma, Experimental / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors; D024502:alpha-Tocopherol / Q000494:pharmacology*
D000975:Antioxidants; D004791:Enzyme Inhibitors; D017382:Reactive Oxygen Species; D004958:Estradiol; D000077584:2-Methoxyestradiol; D013482:Superoxide Dismutase; D024502:alpha-Tocopherol