Chemoprevention efficacy of indole-3-Carbinol in experimentally induced hamster buccal pouch carcinogenesis

Abstract: The aim of the present study was directed to investigate the effect of indole-3-carbinol (I3C) as a new chemopreventive modality in experimentally induced hamster buccal pouch (HBP) carcinogenesis. Material and methods: Twenty five golden Syrian male hamsters five weeks old, weighting 80-120 gs were used as experimental animals and divided into three group(s) (G(S)) (G1, G2 and G3): G1 (negative control): 5 animals were left untreated. G2: (dimethylbenz[a]anthracene (DMBA) painting-HBP group): 10 animals, their right buccal pouches were painted with 0.5% DMBA in paraffin oil 3 times a week and divided into two subgroups, G2A and G2B (G2A which included 5 animals and painted for 8 weeks, G2B which included 5 animals and painted for 14 weeks. G3 (I3C chemoprevention group): 10 hamsters were included in this group were received I3C given by the oral route using a specific vehicle one week before, as well as during the application of DMPA on alternative days for 8 weeks (G3A) and for 14 weeks (G3B). After termination of the experiment, all animals were sacrificed, and the buccal mucosa was excised and fixed in 10% neutral buffered formalin, routinely processed and embedded in paraffin blocks for preparation in order to be examined histologically and immunohistochemically and then statistical analysis based on these examinations was done Results: Gross observations revealed variable features in (G2 and G3) compared to that observed in group G1ranging from normal and smooth surface to fungating tumor masses of large sizes. Histopathological findings revealed variations among chemoprevention groups ranging from normal epithelial layers to epithelial dysplasia to squamous cell carcinoma with invading nests and pearls. Immunohistochemical (IHC) results, regarding Bax expression, revealed variability in the area percentage throughout the groups used. At 8 weeks, area percentages of G1, G2A, and G3A were (39.83%, 22.00 %, and 30.47 %) respectively, and at 14 weeks were (39.83%, 10.45 % and 26.19%) respectively. Bcl2 expressions also had variability in the area percentage throughout the same groups at 8 weeks were (7.05 %, 43.09 % and 18.15 %) respectively, while at 14 weeks they were (7.05 %, 75.21 %and 43.76 %) respectively. Conclusion: I3C is considered as a promising chemotherapeutic agent in prevention of induced HBP carcinogenesis (epithelial dysplasia & invasive carcinoma) and proved beneficial role in improving the outcome by modulating apoptosis and proliferation throughout the process of carcinogenesis.
Keywords: HBP carcinoma, indole-3-carbinol, Bax, Bcl2.