Abstract 563: Chemoprevention of mammary cancer in MMTV-neu transgenic mice by dietary administration of cruciferous vegetable constituent phenethyl isothiocyanate

Abstract

Abstract We have shown previously that phenethyl isothiocyanate (PEITC), which is a highly promising cancer chemopreventive constituent of edible cruciferous vegetables (e.g., watercress), inhibits growth of cultured breast cancer cells in association with apoptosis induction. The present study was undertaken to determine the efficacy of PEITC for prevention of breast cancer using MMTV-neu mouse model. PEITC administration in the diet (3 mmol PEITC/kg AIN76A diet) for 29 weeks caused an approximate 27% decrease in incidence of mammary hyperplasia compared with control, but the difference between control and PEITC treatment groups did not reach statistical significance. On the other hand, incidence of palpable tumors was reduced by about 53% by PEITC administration (P= 0.07 by two-sided Fisher's exact test). Moreover, size of microscopic carcinoma lesions was significantly lower in mice fed PEITC-supplemented diet compared with those fed basal diet (P= 0.05 by two-sided Fisher's exact test). Average body weight of the PEITC-fed mice was modestly but significantly higher than that of control mice at earlier time points (weeks 1-7) but this differential was not observed at later time points (weeks 8-29). Diet consumption was comparable for mice placed on basal diet and PEITC-supplemented diet. Mean PEITC concentration in the plasma and tumor tissue was 901 nM (95% confidence interval- 741-1060 nM) and 87 nmol/kg (95% confidence interval- 67-107 nmol/kg), respectively. Expression of HER-2 oncoprotein as well as number of CD31-positive blood vessels in the tumor did not differ between control and PEITC treatment groups. On the other hand, tumors from PEITC treatment group exhibited about 46% decrease in Ki-67 expression in comparison with control (P= 0.01). Consistent with cellular observations, number of TUNEL-positive apoptotic bodies was about 4.4-fold higher in the tumors of PEITC-fed mice as compared with controls (P= 0.01). Pulmonary metastasis was evident in 3/35 control mice but only 1/32 mice placed on PEITC-supplemented diet exhibited microscopic evidence of metastasis. Size of pulmonary metastasis was also smaller in the PEITC treatment group compared with control. The results indicate that PEITC administration in the diet inhibits carcinoma development in MMTV-neu mice without any signs of overt toxicity. This investigation was supported in part by the US PHS grants CA101753 and CA129347 awarded by the National Cancer Institute. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 563. doi:1538-7445.AM2012-563