No abstract

We previously showed the anticancer property of crocin, a carotenoid isolated and purified from saffron against chemical-induced gastric and breast cancer in rats. In this study, the mechanism of crocin action was investigated in the gastric adenocarcinoma (AGS) cells in comparison with human normal fibroblast skin cells (HFSF-PI3). Crocin revealed a dose- and time-dependent cytotoxic effect against an AGS cell line, as determined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Crocin-induced apoptosis was evidenced by flow cytometry and measuring caspase activity. The increased sub-G1 population and activated caspases in the treated AGS cells confirmed its anticancer effect. Expression of both Bax and Bcl-2 was determined using a semiquantitative reverse transcriptase-polymerase chain reaction and Western blot in these cells before and after treatment with crocin. Apoptosis was significantly stimulated as indicated by increasing the Bax/Bcl-2 ratio after crocin treatment. All of the above-mentioned parameters remained normal in HFSF-PI3 treated with crocin. These data are providing insight into the molecular mechanisms underlying the crocin-induced apoptosis in the AGS cells, rendering it as the potential anticancer agent.

This study investigated the therapeutic effect of crocetin, a carotenoid derived from saffron, on gastric adenocarcinoma (AGS) cells and 1-methyl-3-nitro-1-nitrosoguanidine (MNNG)-induced gastric cancer in rats. An MTT assay showed a significant dose- and time-dependent inhibition of AGS cell proliferation as a result of crocetin administration. Flow cytometry and caspases activity assays revealed apoptosis had been induced in these cells; RT-PCR and Western blot analyses revealed the suppression of Bcl-2 and up-regulation of Bax expression in AGS cells treated with crocetin. These changes were not observed in normal human fibroblast (HFSF-PI3) cells. Pathological study of the tumor tissue in MNNG-induced gastric cancer in rats indicated the dose-dependent inhibition of tumor progression. In addition, crocetin reversed some changed biochemical parameters, including serum antioxidant activity and lactate dehydrogenase in rat serum. The present study demonstrates the antioxidant, anti-proliferative, and apoptotic activities of crocetin against gastric cancer that may benefit human stomach cancer treatment.

Objectives Crocin is derived from dried stigmas of Crocus sativus L. (saffron). It has long been used to prevent and treat various diseases. Although crocin is suggested as one of the most effective cancer therapeutic constituents of saffron stigma, its exact molecular mechanisms are not fully understood. In this study, we reviewed anticancer effects of crocin and its underlying molecular mechanisms. Key findings While several mechanisms may account for the antitumour activity of crocin, alteration of expression/activity of the genes and also epigenetic changes may be considered as necessary phenomena. These alternations may lead to inhibition of cancer cells' proliferation or/and induction of apoptosis through various mechanism including inhibition of synthesis of DNA and RNA, interaction with cellular topoisomerase, suppression of the telomerase activity and active STAT3, and targeting of microtubules. Moreover, this carotenoid could reverse the epithelial-mesenchymal transition and inhibit metastasis. Conclusions Knowing molecular mechanisms of antitumoral agents could guide us to choose the best chemotherapeutic compound especially for targeted therapy and also provide insights about possible side effects.

Crocin and crocetin are two important natural saffron carotenoids, which, along with dimethylcrocetin (DMC) as a semi-synthetic product, are responsible for its color. Many biological properties of saffron have been reported, among which the anticancer property is the most important. Some anticancer drugs have direct interaction with DNA, and thus the present study attempted to investigate the interaction of three major saffron carotenoids-crocin, crocetin, and DMC--with calf thymus DNA (ctDNA) and oligonucleotides. The spectrophotometric data showed some changes in ctDNA absorption spectra due to the formation of complex with saffron extract and each of these three components. Also, all the three components caused the quenching of the fluorescence emission of ctDNA-ethidium bromide complex. The Scatchard analysis of these data indicated a noncompetitive manner for quenching, which is accompanied by the outside groove-binding pattern. The circular dichroism (CD) spectra also indicated the nonintercalative binding and induction of the conformational changes, and B to C transition in ctDNA structure and then unstacking of ctDNA bases at higher concentrations of the carotenoids. The CD spectra of G.C and A.T oligonucleotides after addition of these carotenoids indicated the transition from B- to C-DNA, which is very similar to the ctDNA spectral changes. The DeltaG(H(2)O), the best parameter for the estimation of macromolecule stability, was determined for ctDNA denaturation using dodecyl trimethylammonium bromide in the absence and presence of crocin, crocetin, or DMC. Our results showed a decrease in the Delta G(H(2)O), indicating the ctDNA destabilization due to its interaction with the mentioned ligands. In conclusion, the results show that saffron and its carotenoids interact with DNA and induce some conformational changes in it. Of these carotenoids, the order of potential of interaction with DNA is crocetin > DMC >> crocin.