THE ANTITUMOR ACTIVITY OF THYMOQUINONE AND THYMOHYDROQUINONE IN VITRO AND IN VIVO
S. Ivankovic1, R. Stojkovic1, *, M. Jukic2,
M. Milos2, M. Milos3 M. Jurin1
1Division of Molecular Medicine, Rudjer Boskovic Institute, 10000 Zagreb, Croatia
2Department of Biochemistry and Food chemistry, Faculty of Chemical Technology, 21000 Split, Croatia
3Faculty of Sciences, Department of Physical Chemistry, University of Geneva, 1204 Geneva, Switzerland
Abstract. Aim: The aim of the study was to investigate antitumor activity of
thymoquinone (TQ) and thymohydroquinone (THQ) in vitro and in vivo. Materials
and Methods: In the in vitro experiments, L929 mouse ?broblasts and two tumor
cell lines (squamous cell carcinoma (SCC VII) and fibrosarcoma (FsaR)) were used. The
cells were cultured with 0.1 or 0.01 mg/ml TQ or THQ for 24 h, and cytotoxicity assay was
performed with the use of crystal violet staining technique. For in vivo antitumor
efficiency evaluation of new compounds two murine tumor models (fibrosarcoma (FsaR) and
squamous cell carcinoma (SCC VII)) were used. The used dose was equal for both substances.
Antitumor effect of 4 intratumoral injections of TQ and THQ at the dose of 5 mg/kg was
evaluated by comparison of tumor growth kinetics between treated and control animals. Results:In vitro study showed that TQ and THQ exhibit statistically significant cytotoxic
activity (p < 0.01). The cytotoxic activity was dose dependent and more
expressed against tumor cells than against L929 fibroblasts. The result of antitumor
activities of TQ and THQ in vivo reached TGI = 52% and it was statistically
significant (p < 0.05). Conclusion: The results indicate that THQ
antitumor activity may be improved with further dose increase of the investigated
substance.
Key Words:thymoquinone, thymohydroquinone, antitumor activity, in
vitro, in vivo, mice