Abstract
Crocin, a component of saffron spice, is known to have an anticancer activity. However, the targets of crocin are not known. In this study, crocin was found to inhibit the proliferation of HCC70, HCC1806, HeLa and CCD1059sk cells by targeting microtubules. Crocin depolymerized both the interphase and mitotic microtubules of different cancer cells, inhibited mitosis and induced multipolar spindle formation in these cells. In vitro, crocin inhibited the assembly of pure tubulin as well as the assembly of microtubule-associated protein rich tubulin. Electron microscopic analysis showed that crocin inhibited microtubule assembly while it induced aggregation of tubulin at higher concentrations. Crocin co-eluted with tubulin suggesting that it binds to tubulin. Vinblastine inhibited the binding of crocin to tubulin while podophyllotoxin did not inhibit the crocin binding indicating that crocin binds at the vinblastine site on tubulin. The results suggested that crocin inhibited cell proliferation mainly by disrupting the microtubule network.
Highlights
The digentiobiosyl ester of crocetin–α-crocin is a major component of saffron spice, derived from Crocus sativus L
The treatment of cells with crocin led to the formation of multipolar spindles with distorted chromosomes and centrosome fragmentation similar to the cells treated with well-known anti-mitotic drugs such as vinblastine, paclitaxel and cryptophycin 5221
The results indicated that the anti-proliferative action of crocin involves perturbation of mitosis in cancer cells
Summary
The digentiobiosyl ester of crocetin–α-crocin is a major component of saffron spice, derived from Crocus sativus L. Crocin was found to inhibit cell cycle progression and to induce apoptosis[11]. Crocin has been shown to induce apoptosis in tumor cells by down-regulating the expression of Bcl-2, survivin, cyclin D1 and up-regulating the expression of Bax in BALB/c xenograft tumor[15]. It was indicated that crocin interacts with tubulin in a manner that increases the polymerization of microtubules in vitro[20], the interaction within the cells has not yet been elucidated. The evidence presented in the present work indicated that crocin inhibits cell proliferation by targeting tubulin. These results suggest that crocin has a potential to be developed as an anticancer agent
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