Human
ovarian cancer cells specifically bind the
isoflavone daidzein. A chemical conjugate between
daidzein and the garlic
enzyme alliinase was prepared. The conjugate specifically bound to
ovarian cancer cells and upon addition of the
prodrug alliin, it effectively produced cytotoxic
allicin molecules which killed the
cancer cells. In vivo targeting and antitumor effect was confirmed by NIR and bioluminescence imaging using daidzein-alliinase-CyTE-777 conjugates and
luciferase-expressing
ovarian cancer cells. Co-localization of the fluorescent conjugate with bioluminescence was observed for intraperitoneal
tumors while nonconjugated
alliinase did not accumulate. Biodistribution studies with
Europium-labeled conjugate revealed a five fold higher uptake in
tumors as compared to other tissues. Treatment of
tumor bearing mice with
daidzein-
alliinase and
alliin effectively attenuated
tumor progression during the first 12 days while a 5-fold increase in bioluminescence was detected in placebo-treated animals. Autopsy revealed only small individual foci of luminescence at the site of
tumor cells inoculation. Histological examination of organs and tissues did not reveal any additional foci of
carcinoma or signs of toxicity. These results suggest that the targeted
alliinase conjugates in the presence of
alliin, generated therapeutically effective levels of
allicin which were capable of suppressing
tumor progression of intraperitoneal
ovarian cancer in an animal model.