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In Vivo Anti-tumor Activity of 3-Methyl-6-allylthiopyridazine in Nude Mice Xenografted with Hep-G2 Hepatocarcinoma

Kwon, Soon-Kyoung   (College of Pharmacy, Duksung Women's UniversityUU0000446  ); Moon, Aree   (College of Pharmacy, Duksung Women's UniversityUU0000446  );
  • 초록

    Organosulfur compounds have been shown to exert an anti-cancer activity. In an attempt to develop novel chemopreventive and anti-cancer agents for liver cancer, we synthesized allylthiopyridazine derivatives. We have previously shown that allylthiopyridazine derivatives exert inhibitory effects on proliferation, invasion and migration of SK-Hep-1 hepatocarcinoma cells in vitro. The in vivo anti-tumor effect of 3-methvl-6-allylthiopy-ridazine, named as K6, was also reported. In this study, we further investigated the preclinical anti-cancer efficacy of K6 for hepatocarcinoma using nude mice xenografted with Hep-G2 hepatocellular carcinoma cells. K6(20-100 mg/kg, orally administered everyday for 30 days) markedly decreased the tumor volume of Hep-G2 cell-transplanted nude mice as evidenced by ultrasonographic and plethysmogranhic analyses. The inhibitory effect on tumor volume was lower than that exerted by doxorubicin (2 mg/kg), intravenously injected) which was used as a positive control. This study shows that K6 efficiently suppresses xenograft tumor growth, revealing K6 as apotential anti-cancer agent for suppressing in vivo progression of liver cancer. Given that hepatocarcinoma is among the most prevalent and lethal malignancies and there is no effective treatment to date, our study may contribute to the potential drug development for liver cancer.


  • 주제어

    Allylthiopyridazine .   hepatocarcinoma .   xenograft.  

  • 참고문헌 (20)

    1. Bandoh, K., Ishizuka, Y. and Sato, M. (1995). Effects of 3-[N(2-Chlorobenzyl)amino]-6-(1H-imidazol-l-yl) pyridazine dihydrochloride on various aromatase enzyme systems and experimental breast cancer. Arzneim-Forsch.(Drug Res.) 45, 897-900. 
    2. Chai, H.-Y., Sin, J. S., Kim, T. M., Kwon, W., Cho, Y. M., Choi, E.-K., Hwang, S.-Y., Kim, Y.-B., Moon, A., Kwon, S.-K. and Kang, J.-K. (2004). Antitumor activity of pyridazine derivative in nude mice. Kor. J Lab. Animal Sci. 20, 68-75 
    3. Cho, M. K. and Kim, S. G. (1998). Differential induction of rat hepatic microsomal epoxide hydrolase and rGSTA2 by diazines: the role of cytochrome P450 2E I-mediated metabolic activation. Chem. Biol. Interact. 116, 229-245 
    4. Clapper, M. L. (1998). Chemopreventive activity of oltipras. Pharma. Ther. 53, 17-27 
    5. Elka, H. K., Vincent, E. L. O. and Fung, K. P. (2002). Circumvention of multidrug resistance and reduction of cardiotoxicity of doxorubicin in vivo by coupling it with low density lipoprotein. Lift Sci. 73, 677-687 
    6. Goluboff, E. T., Shabsigh, A., Saidi, J. A., et al., (1999). Exisulind (sulindac sulfone) suppresses growth of human prostate cancer in a nude mouse xenograft model by increasing apoptosis. Urol. 53, 440-445 
    7. Imahie, H., Adachi, T., Nagasaki, T., Yamamura, T. and Hori, M. (1995). Effects of adriamycin, anticancer drug showing testicular toxicity, on fertility in male rats. J Toxicol. Sci. 20, 183-193 
    8. Jung, M. Y., Kwon, S. K. and Moon, A. (2001). Chemopreventive allylthiopyridazine derivatives induced apoptosis in SK-Hep-l hepatocarcinoma cells through a caspase-3-dependent mechanism. Eur. J Cancer 37, 2104-2110 
    9. Kelland, L. R. (2004). Of mice and men: values and liabilities of the athymic nude mouse model in anticancer drug development. Eur. J Cancer 40, 827-836 
    10. Kwon, S. K. and Hyun, J. W. (2000). Synthesis of allylthiopyridazine derivatives and their protective effects of UV-C irradiation. J Pharm. Soc. Kor. 44,9-15 
    11. Kwon, S. K. (2000). Pyridazine derivatives developed as medicines. J Applied Pharmacol. 8, 1-12 
    12. Kwon, S. K. (2003). Organosulfur compounds from Allium sativum and physiological activities. J Applied Pharmacol., 11, 8-32 
    13. Labonte, P, Kadhim, S., Bowlin, T. and Mounir, S. (2000). Inhibition of tumor growth with doxorubicin in a new orthotopically impaired human hepatocellular carcinoma model. Hepatol. Res. 18, 72-85 
    14. Langdon, S. P. and Hendricks (1994). Preclinical phase studies in human tumor xenografts. Eur. Multicenter Follow-up Study 5, 415-422 
    15. Lee, E. J., Shin, I., Kwon, S. -K., Shin, H. -S. and Moon. A. (2003). Chemopreventive allylthiopyridazines inhibit invasion, migration and angiogenesis in hepatocarcinoma cells. Int. J. Oneal. 23, 1645-1650 
    16. Rao, C. V., Rivenson, A., Simi, B., et al., (1995). Chemoprevention of colon carcinogensis by sulindac, a nonsteroidal anti-inflamantory agent. Cancer 55, 1464-1472 
    17. Shin, H. S. and Kwon, S. K. (2003). Synthesis of allylthiopyridazine derivatives and inhibition of aflatoxin Bl-induced hepatoxicity in rats. Architecture Pharma. Res. 5, 351-357 
    18. Williams, P. L., James, R. C. and Roberts, S. M. (2000). Principles of toxicology. John Wiley & Sons, Inc. 2, 209-217 
    19. Yang, E. B., Tang, W. Y., Zhang, K., Cheng, L. Y, et al., (1997). Norcantharidin inhibits growth of human Hep-G2 cell-transplanted tumor in nude mice and prolongs host survival. Cancer Lett. 117. 93-98 
    20. Bibby, M. C. (2004). Orthototic models of cancer for preclinical drug evaluation: advantages and disadvantages. Eur. J Cancer 40, 852-857 

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  • Moon, Aree (15)

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