Abstract A148: Concomitant activation of pro- and antiproliferative mechanisms abrogate tumor growth inhibition by kale sprout intervention in a human prostate cancer xenograft model

Abstract

Abstract Cruciferous vegetables are rich in glucosinolates, which are converted to isothiocyanates (ITCs) and indole-based compounds by the enzymatic activity of myrosinase. Tumor-growth inhibitory efficacy of purified constituents derived from cruciferous vegetables has been demonstrated in animal models at various organ sites including the prostate. However, except induction of detoxifying enzymes, relatively little is known on mechanisms affected by dietary intervention with cruciferous vegetables, which represent a mixture of various constituents potentially enhancing or blocking their activities (Pappa et al., 2007). In the present study, we tested the tumor growth inhibitory potential of kale sprouts in a human prostate cancer xenograft model. LNCaP human prostate cancer cells were injected to male nude Balb/c mice (10 per group). Mice were fed with either regular rodent chow or chow supplemented with 20% kale sprouts (containing about 60 µmol glucosinolates per 5 g chow consumed daily, together with active myrosinase) from a week before cell injection until sacrifice after 7.5 weeks of intervention. Compared with normal diet, kale sprout intervention did not significantly inhibit average tumor weights. Secreted prostate specific antigen (PSA), which is used as a biomarker for prostate cancer, was highly correlated with tumor size in both intervention groups. Interestingly however, plasma PSA levels in the kale sprout group were 2.5-fold higher (p<0.05) than in the control group. In tumor tissue, mRNA expression of hormone-regulated genes such as PSA, androgen receptor, insulin-like growth factor-1 and its receptor were significantly increased. We also observed an increase in histone H4 acetylation, which was not linked to inhibition of HDAC activity. As a consequence however, p21 mRNA and protein expression was upregulated by kale sprout intervention. In addition, although there was no difference in the expression of PCNA as a proliferation marker, phosphorylated histone H3 staining as an indication of mitotic arrest was enhance in the kale sprout group. Interestingly, hemoglobin levels in tumor cell lysate, and vessels in tumor sections were significantly reduced by consuming kale sprout powder, indicating anti-angiogenic potential. This was associated with downregulated VEGF-c mRNA expression. Overall, our in vivo study indicates that components in kale sprouts or their metabolites concomitantly affect both anti-proliferative (histone H4 acetylation, cell cycle arrest, anti-angiogenesis) and pro-proliferative mechanisms (hormone signaling), which in combination may abrogate inhibitory effects on tumor growth. These data may contribute to a better understanding of the effects of cruciferous vegetable consumption in cancer prevention. Citation Information: Cancer Prev Res 2010;3(1 Suppl):A148.