Based on the potential of
resveratrol as a
colon cancer chemopreventive agent, a set of 26
stilbenes were synthesized and tested against the
colon cancer cell lines HT-29 and Caco-2. (Z)-4-(3,5-Dimethoxystyryl)aniline (4), (Z)-methyl-4-(3,5-dimethoxystyryl)benzoate (6), and (Z)-1,3-dimethoxy-5-(4-methoxystyryl)benzene (10) showed strong inhibitory activity in vitro. In vivo studies using HT-29 xenografts in immunodeficient mice were conducted with 4, 6 and 10, together with their corresponding trans isomers (3, 5, and 9, respectively), at the dose of 10 mg/kg
body weight.
Tumor volume was significantly lowered in 3-, 4-, and 9-treated groups. The cis- and trans-amino analogs (4 and 3, respectively) had similar effect on
tumor growth, a 40% decrease compared to the control. Analysis of the serum revealed that 4 isomerized to 3, which may explain their similar effects in SCID mice.
Stilbenes 5, 6, 9, and 10 retained their configurations in the serum.
Stilbenes 6 and 10 lacked
tumor-suppressive effect in SCID mice; the serum levels of these analogs were low (18.8 and 15.5 ng/mL, respectively).
Stilbene 9, while weakly active in vitro demonstrated good activity in vivo, was found at higher levels in the serum (69.9 ng/mL) compared to 10. The anti-tumorigenic activity of these
stilbene analogs may be partly linked to their effects on
proteins involved in cell proliferation, as observed by lowered expression of
proliferating cell nuclear antigen and upregulation of the
cyclin-dependent kinase inhibitor, p27, in the
tumor tissues. Overall, identification of the anti-tumorigenic potential of these compounds provides opportunities for their use against
colorectal cancer.