Investigation of the redox status in H22 hepatocellular carcinoma xenografts treated by a novel anticancer drug——ethaselen

Abstract

Abstract:

We investigated the redox status of H22 hepatocellular carcinoma xenografts treated with various doses of ethaselen, a novel anticancer drug targeting thioredoxin reductase (TrxR). The concentrations of low molecular weight antioxidant glutathione (GSH) and malondialdehyde (MDA), a product of lipid peroxidation, as well as the activities of important antioxidant enzymes were measured for elucidating the redox status of H22 tumor tissues. We found that the decreased GSH level, decreased thioredoxin reductase and superoxide dismutase (SOD) activities as well as increased MDA content were closely related to the tumor growth inhibition and ethaselen doses. Glutathione peroxidase (GPx) and glutathione reductase (GR) activities are also affected by ethaselen treatment. However, the catalase (CAT) activity remains unchanged. Finally, we studied the relationship of tumor growth inhibition caused by ethaselen with these redox factors. This study showed that ethaselen could elevate the oxidative stress to suppress the H22 tumor growth in mice model.

Key words: Ethaselen, Ethaselen, Thioredoxin reductase inhibitor, Thioredoxin reductase inhibitor, Anticancer drug, Anticancer drug, Redox status, Redox status, Antioxidant system, Antioxidant system, Hepatocellular carcinoma, Hepatocellular carcinoma

CLC Number:

R969.1

Supporting:

Li-Hui Wang^1,2, Hui-Hui Zeng^1,2* . Investigation of the redox status in H22 hepatocellular carcinoma xenografts treated by a novel anticancer drug——ethaselen[J]. .

References

[1] Helene, P.; Dennis, C.; Peng, H. Drug Resist. Updat. 2004, 7, 97-110.
[2] Burdon, R.H. Free Radic. Biol. Med. 1995, 18, 775-794.
[3] Schimmel, M.; Bauer, G. Oncogene. 2002, 21, 5886-5896.
[4] Dipple, A. Carcinogenesis. 1995, 16, 437-441.
[5] Dizdaroglu, M. Free Rad. Biol. Med. 1991, 10, 225-242.
[6] Kong, Q.; Beel, J.A.; Lillehei, K.O. Med. Hypotheses. 2000, 55, 29-35.
[7] Kong, Q.; Lillehei, K.O. Med. Hypotheses. 1998, 51, 405-409.
[8] Miyajima, A.; Nakashima, J.; Yoshioka, K.; Tachibana, M.; Tazaki, H.; Murai, M. Br. J. Cancer. 1997, 76, 206-210.
[9] Valko, M.; Rhodes, C.J.; Moncol, J.; Izakovic, M.; Mazur, M. Chem. Biol. Interact. 2006, 160, 1-40.
[10] Zhao, F.; Yan, J.; Deng, S.; Lan, L.; He, F.; Kuang, B.; Zeng, H. Cancer Lett. 2006, 236, 46-53.
[11] Shi, C.; Yu, L.Z.; Yang, F.G.; Yan, J.; Zeng, H.H. Biochem. Biophys. Res. Commun. 2003, 309, 578-583.
[12] Xing, F.; Li, S.; Ge, X.; Wang, C.; Zeng, H.; Li, D.; Dong, L. Oral. Oncol. 2008, 44, 963-969.
[13] Peng, Z.F.; Lan, L.X.; Zhao, F.; Li, J.; Tan, Q.; Yin, H.W.; Zeng, H.H. J. Zhejiang Univ. Sci. B. 2008, 9, 16-21.
[14] Tan. Q.; Li, J.; Yin, H.W.; Wang, L.H.; Tang, W.C.; Zhao, F. Liu, X.M.; Zeng, H.H. Invest. New Drugs. 2009, in press.
[15] Lan, L.X.; Zhao, F.; Wang, Y.; Zeng, H.H. Eur. J. Pharmacol. 2007, 555, 83-92.
[16] Arnér, E.S.; Holmgren, A. Semin. Cancer Biol. 2006, 16, 420-426.
[17] Urig, S.; Becker, K. Semin. Cancer Biol. 2006, 16, 452-465.
[18] Paul, J.H.; Russell, H. Anal. Biochem. 1976, 74, 214-226.
[19] Placer, Z.A.; Cushman, L.L.; Johnson, B.C. Anal. Biochem. 1966, 16, 359-364.
[20] Wang, Y.M.; Qiao, M.; Mieyal, J.J.; Asmis, L.M.; Asmis, R. Free Radic. Biol. Med. 2006, 41, 775-785.
[21] Holmgren, A.; Bjornstedt, M. Methods Enzymol. 1995, 252, 199-208.
[22] Lawrence, R.A.; Burk, R.F. Biochem. Biophys. Res. Commun. 1976, 71, 952-958.
[23] Szilágyi, I.; Labádi, I.; Hernadi, K.; Pálinkó, I.; Nagy, N.V.; Korecz, L.; Rockenbauer, A.; Kele, Z.; Kiss, T. J. Inorg. Biochem. 2005, 99, 1619-1629.
[24] Zhang, J.; Lu, H. Free Radic. Biol. Med. 2007, 43, 1574-1583.
[25] Schafer, F.Q.; Buettner, G.R. Free Rad. Biol. Med. 2001, 30, 1191-1212.
[26] Garcon, G.; Zerimech, F.; Hannothiaux, M.; Gosset, P.; Martin, A. Marez, T.; Shirali, P. Toxicology. 2001, 166, 129-137.
[27] Green, D.R.; Reed, J.C. Science. 1998, 281, 1309-1312.
[28] Pennington, J.D.; Jacobs, K.M.; Sun, L.; Bar-Sela, G.; Mishra, M.; Gius, D. Curr. Pharm. Design. 2007, 13, 3368-3377.
[29] Gromer, S.; Urig, S.; Becker, K. Med. Res. Rev. 2004, 24, 40-89.
[30] Koc, A.; Mathews, C.K.; Wheeler, L.J.; Gross, M.K.; Merrill, G.F. J. Biol. Chem. 2006, 281, 15058-15063.
[31] Kim, C.; Cha, Y.N. Adv. Exp. Med. Biol. 2009, 643, 463-472.