Effects of curcumin on bleomycin-induced apoptosis in human malignant testicular germ cells
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ORIGINAL PAPER
Effects of curcumin on bleomycin-induced apoptosis in human malignant testicular germ cells Aysegul Cort & Mujgan Timur & Evrim Ozdemir & Tomris Ozben
Received: 17 April 2012 / Accepted: 9 September 2012 / Published online: 23 September 2012 # University of Navarra 2012
Abstract Testicular cancer is the most common cancer among young men of reproductive age. Bleomycin is a frequently used drug for the treatment of several malignancies and is part of the chemotherapy protocols in testicular cancer. Bleomycin causes an increase in oxidative stress which has been shown to induce apoptosis in cancer cells. Curcumin (diferuloylmethane), an active component of the spice turmeric, has attracted interest because of its anti-inflammatory and chemopreventive activities. However, no study has been carried out so far to elucidate its interaction with bleomycin in testicular cancer cells. In this study, we investigated the effects of curcumin and bleomycin on apoptosis signalling pathways and compared the effects of bleomycin with H2O2 which directly produces reactive oxygen species. We measured apoptosis markers such as caspase-3, caspase-8, and caspase-9 activities and Bcl-2, Bax, and Cyt-c levels in NCCIT cells incubated with curcumin (5 μM), bleomycin (120 μg/ml), bleomycin + curcumin, H2O2 (35 μM), and H2O2 + curcumin for 72 h. Curcumin, bleomycin, and H2O2 caused apoptosis indicated as increases in caspase-3, caspase-8, and caspase-9 activities and Bax and cytoplasmic Cyt-c levels and a decrease in Bcl-2 level. Concurrent use of curcumin with bleomycin decreased caspase activities and Bax A. Cort : M. Timur : E. Ozdemir : T. Ozben (*) Department of Biochemistry, Faculty of Medicine, Akdeniz University, 07070 Antalya, Turkey e-mail: [email protected]
and Cyt-c levels compared to their separate effects in NCCIT cells. Our findings suggest that concurrent use of curcumin during chemotherapy in testis cancer should be avoided due to the inhibitory effect of curcumin on bleomycin-induced apoptosis. Keywords Testicular cancer . NCCITcell . Apoptosis . Bleomycin . Curcumin
Introduction Testicular germ cell tumors are the most common malignancy in young men. The incidence has risen over the last century with a peak incidence between 20 and 40 years of age [12]. Bleomycin is approved by FDA to be used alone or with other drugs as palliative treatment of testicular cancer. Bleomycin is an essential component of the cisplatin-based chemotherapy regimens used effectively in the treatment of testicular cancer [8]. Bleomycin induces the highest level of oxidative stress. This is due to their unique ability to generate reactive oxygen species in mitochondria. Numerous in vitro studies have demonstrated that a wide range of anticancer agents including bleomycin induce apoptosis in malignant cells by generating reactive oxygen species (ROS). Free radical generation and subsequent oxidative stress mediate bleomycin’s cytotoxic effects in cancer cells via inducing apoptosis. There are numerous studies in the literature
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