Effects of long-term treatment of colon adenocarcinoma with crocin, a carotenoid from saffron (Crocus sativus L.): an experimental study in the rat

We used an experimental model in the rat to examine the effects of long-ter m treatment with crocin, a glycosylated carotenoid from the stigmas of the saffron crocus, on colon cancer. BD-IX rats were divided into four groups. Groups GI and G2, designated "cancer groups," were used to study the effect s of crocin on the progression of colon cancer, and Groups G3 and G4, desig nated "toxicity groups, " were used to study the effects of the treatment o n metabolic processes and the parenchyma. DHD/K12-PROb cells were injected subcutaneously into the chest of Group G1 and G2 animals. From 1 to 13 week after inoculation, animals in Groups G2 and G4 received a weekly injection of crocin (400 mg/kg body wt sc). Animals in Groups GI and G3 received no treatment. In addition, lines of animal and human colon adenocarcinoma cell s (DHD/K12-PROb and HT-29) were used to perform assays in vitro to examine the cytotoxicity of crocin. Life span was extended and tumor growth was slo wer in crocin-treated female rats, but no significant antitumor effect was found in male rats. Acute tubular necrosis was found in all kidney samples from crocin-treated animals, but slight signs of nephrotoxicity were found by biochemical analysis of the serum. In assays in vitro, crocin had a pote nt cytotoxic effect on human and animal adenocarcinoma cells (HT-29 and DHD /K12-PROb cells, 50% lethal dose = 0.4 and 1.0 mM, respectively). Treated c ells exhibited a remarkable loss of cytoplasm and wide cytoplasmic vacuole- like areas. In conclusion, long-term treatment with crocin enhances surviva l selectively in female rats with colon cancer without major toxic effects. The effects of crocin might be related to its strong cytotoxic effect on c ultured tumor cells.