Effects of Long-Term Treatment of Colon Adenocarcinoma With Crocin, a Carotenoid From Saffron (Crocus sativus L.): An Experimental Study in the Rat

Abstract

We used an experimental model in the rat to examine the effects of long-term 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 G1 and G2, designated "cancer groups," were used to study the effects of crocin on the progression of colon cancer, and Groups G3 and G4, designated "toxicity groups," were used to study the effects of the treatment on 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 weeks after inoculation, animals in Groups G2 and G4 received a weekly injection of crocin (400 mg/kg body wt s.c.). Animals in Groups G1 and G3 received no treatment. In addition, lines of animal and human colon adenocarcinoma cells (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 slower 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 potent 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 cells exhibited a remarkable loss of cytoplasm and wide cytoplasmic vacuole-like areas. In conclusion, long-term treatment with crocin enhances survival selectively in female rats with colon cancer without major toxic effects. The effects of crocin might be related to its strong cytotoxic effect on cultured tumor cells.

Protective Effect of Crocus sativus Stigma Extract and Crocin (trans-crocin 4) on Methyl Methanesulfonate–Induced DNA Damage in Mice Organs

“…Abdullaev and Frenkel also showed that saffron could exert inhibitory effect on cellular DNA and RNA synthesis, but not on protein synthesis Frenkel, 1992a, 1992b). Cancer chemopreventive as well as antitumor activities were also reported for crocins and crocetin derivatives in different assay systems (Tarantilis et al, 1994;Wang et al, 1995;Escribano et al, 1996;Konoshima et al, 1998;Garcia-Olmo et al, 1999;Aung et al, 2007).…”

The role of herbs and spices in cancer prevention

“…Saffron, and some of its bioactive components, have also been shown to possess antitumor activity, but as observed in the research with cumin seeds, varied responses to saffron and its bioactive components have been observed in different types of cultured malignant cells (97). There also been a differential response noted between male and female rats with colon adenocarcinomas to crocin (a compound in saffron) which indicates the potential involvement of hormonal factors in tumorigenesis (98).…”

Saffron: a natural product with potential pharmaceutical applications

“…[1,3,[7][8][9][10][11][12][13][14] In parallel, the possible uses of saffron and its active constituents lead to an increasing number of research studies, some of which have drawn some very useful and intriguing results of active ingredients of saffron, especially against malignancies, cardiovascular and Alzheimer's disease. [15][16][17][18][19][20][21][22] In this minireview, we aim to summarize and critically address previous and current evidence regarding the biological/ pharmacological activities of saffron and its active ingredients and their possible therapeutic uses. The history and structural features of saffron constituents are given in the first part of the review, followed by a comprehensive and critical presentation of the published preclinical and clinical studies and review papers on the pharmacology and potential therapeutic applications of saffron and its main active components.…”