Effects of curcumin on bleomycin-induced apoptosis in human malignant testicular germ cells
- 296 Downloads
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 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.
KeywordsTesticular cancer NCCIT cell Apoptosis Bleomycin Curcumin
This study was supported by Scientific and Technological Research Council, Turkey (TUBITAK) (COST-CM0603-15) and Akdeniz University.
Conflict of interest
The authors report no conflicts of interest. The content is solely the responsibility of the authors.
- 6.Cort A, Timur M, Ozdemir E, Kucuksayan E, Ozben T (2012) Synergistic anticancer activity of curcumin and bleomycin: an in vitro study using human malignant testicular germ cells. Mol Med Report 5:1481–1486Google Scholar
- 8.de Wit R, Stoter G, Kaye SB, Sleijfer DT, Jones WG, ten Bokkel Huinink WW, Rea LA, Collette L, Sylvester R (1997) Importance of bleomycin in combination chemotherapy for good-prognosis testicular nonseminoma: a randomized study of the European Organization for Research and Treatment of Cancer Genitourinary Tract Cancer Cooperative Group. J Clin Oncol 15:1837–1843PubMedGoogle Scholar
- 9.Garcea G, Berry DP, Jones DJ, Singh R, Dennison AR, Farmer PB, Sharma RA, Steward WP, Gescher AJ (2005) Consumption of the putative chemopreventive agent curcumin by cancer patients: assessment of curcumin levels in the colorectum and their pharmacodynamic consequences. Cancer Epidemiol Biomarkers Prev 14:120–125PubMedGoogle Scholar
- 11.Huang AC, Chang CL, Yu CS, Chen PY, Yang JS, Ji BC, Lin TP, Chiu CF, Yeh SP, Huang YP, Lien JC, Chung JG (2011) Induction of apoptosis by curcumin in murine myelomonocytic leukemia WEHI-3 cells is mediated via endoplasmic reticulum stress and mitochondria-dependent pathways. Environ Toxicol. doi: 10.1002/tox.20716
- 13.Ip SW, Wu SY, Yu CC, Kuo CL, Yu CS, Yang JS, Lin ZP, Chiou SM, Chung HK, Ho HC, Chung JG (2011) Induction of apoptotic death by curcumin in human tongue squamous cell carcinoma SCC-4 cells is mediated through endoplasmic reticulum stress and mitochondria-dependent pathways. Cell Biochem Funct 29:641–650PubMedCrossRefGoogle Scholar
- 17.Lee JW, Hong HM, Kwon DD, Pae HO, Jeong HJ (2010) Dimethoxycurcumin, a structural analogue of curcumin, induces apoptosis in human renal carcinoma caki cells through the production of reactive oxygen species, the release of cytochrome C, and the activation of caspase-3. Kor J Urol 51:870–878CrossRefGoogle Scholar
- 18.Lin SS, Lai KC, Hsu SC, Yang JS, Kuo CL, Lin JP, Ma YS, Wu CC, Chung JG (2009) Curcumin inhibits the migration and invasion of human A549 lung cancer cells through the inhibition of matrix metalloproteinase-2 and -9 and vascular endothelial growth factor (VEGF). Cancer Lett 285:127–133PubMedCrossRefGoogle Scholar
- 24.Rao J, Xu DR, Zheng FM, Long ZJ, Huang SS, Wu X, Zhou WH, Huang RW, Liu Q (2011) Curcumin reduces expression of Bcl-2, leading to apoptosis in daunorubicin-insensitive CD34+ acute myeloid leukemia cell lines and primary sorted CD34+ acute myeloid leukemia cells. J Transl Med 9:71PubMedCrossRefGoogle Scholar
- 25.Sharma RA, Ireson CR, Verschoyle RD, Hill KA, Williams ML, Leuratti C, Manson MM, Marnett LJ, Steward WP, Gescher A (2001) Effects of dietary curcumin on glutathione S-transferase and malondialdehyde-DNA adducts in rat liver and colon mucosa: relationship with drug levels. Clin Cancer Res 7:1452–1458PubMedGoogle Scholar
- 34.Wu SH, Hang LW, Yang JS, Chen HY, Lin HY, Chiang JH, Lu CC, Yang JL, Lai TY, Ko YC, Chung JG (2010) Curcumin induces apoptosis in human non-small cell lung cancer NCI-H460 cells through ER stress and caspase cascade- and mitochondria-dependent pathways. Anticancer Res 30:2125–2133PubMedGoogle Scholar
- 38.Zhang X, Zhang HQ, Zhu GH, Wang YH, Yu XC, Zhu XB, Liang G, Xiao J, Li XK (2012) A novel mono-carbonyl analogue of curcumin induces apoptosis in ovarian carcinoma cells via endoplasmic reticulum stress and reactive oxygen species production. Mol Med Report 5:739–744Google Scholar