Assessment of antitumor effect of 2-(6,8-dimethyl-5-nitro-4-chloroquinoline-2-yl)-5,6,7-trichloro-1,3-tropolone in subcutaneous xenografts of A-549 tumor cell culture.

Abstract

e20520 Background: The aim of the study was an assessment of antitumor effect of 2-(6,8-dimethyl-5-nitro-4-chloroquinoline-2-yl)-5,6,7-trichloro-1,3-tropolone for subcutaneous xenografts of A-549 lung tumor cells in immunodeficient Balb/c Nude mice. Methods: 2-(6,8-dimethyl-5-nitro-4-chloroquinoline-2-yl)-5,6,7-trichloro-1,3-tropolone is a new compound in the series of 2-quinoline-2-yl-1,3-tropolone derivatives. The study included 50 immunodeficient Balb/c Nude mice divided into 5 groups depending on the dosage of the studied substance (0.0055; 0.055; 0.55 and 2.75 mg/g). The A-549 cells of lung cancer were used as the xenograft. Antitumor effect of tropolone was evaluated by the inhibition of tumor growth (ITG%) and the index of tumor growth (I). The experiment lasted for 36 days starting from the first administration of substances. Results: Indicators of the average tumor volume on day 36 of the experiment in experimental groups 1, 2, 3 and 4 and in the control group were 678.9; 952.3; 1746.4; 2150.8 and 2729.5 mm3, respectively. The indices of tumor growth in groups 1, 2, 3 and 4 were statistically significantly lower than in group 5 (controls) starting from days 15, 21, 21 and 24, respectively, and until the end of the experiment. Maximal differences between groups 1 and 5 were observed on days 33 and 36 – by 3.7 (p = 0.01) and 4.1 (p = 0.003) times, respectively. Antitumor effect of 2-(6,8-dimethyl-5-nitro-4-chloroquinoline-2-yl)-5,6,7-trichloro-1,3-tropolone demonstrated by the study could be associated with various mechanisms. For example, its closely related compound – hinoktiol, according to numerous studies, has a cytotoxic effect associated with stopping the cell cycle, induction of apoptosis, DNA damage, and autophagic death of tumor cells. Conclusions: The study demonstrated statistically significant differences in xenograft volumes between all experimental groups and the control group. 2.75 mg/g of mouse weight was the most effective dosage of the studied compound leading to a slow decrease in tumor growth rates and a decrease in the volumes of subcutaneous xenografts.