earticle

영어

Anticancer effects of crocin, a major carotenoid in stigma of Crocus sativus L, and crocetin, precursor of crocin, were investigated to obtain different effects derived from two different structures. Cytotoxicity of crocin/crocetin on five human cancer cell lines was monitored and crocetin showed higher cytotoxicity than crocin on all five tested cell lines. FACS analysis showed the generation of cellular ROS stimulated by 1 mM crocetin in HeLa cells after treatment of 24 and 48 h. HeLa cell viability was restored up to 83.5 ± 7.3 (p <0.05) compared to control cells when 7 mM N-acetylcysteine (NAC) was co-treated as an antioxidant with crocetin, whereas NAC exhibited slight recovery on viability of crocin treated HeLa cells. Reporter assay of Nrf2 (NF-E2-related factor 2) revealed activation of Nrf2 in HeLa cells induced by crocin/crocetin treatment. 1 mM crocetin caused 3.0 ± 0.3 (p <0.001) folds increase while 800 μM crocin induced 1.6 ± 0.1 (p <0.05) folds increase of Nrf2 in HeLa cells. Activation of Nrf2 supported by induced expression level of mRNA and protein of phase II detoxifying enzymes such as heme oxigenase-1 (HO-1) and NAD(P)H:quinine oxidoreductase-1 (NQO-1). Finally, inhibitory effect of crocin/crocetin on LDHA in HeLa cells was observed both expression level and activity. Crocetin repressed 34.2 % activity of LDHA compared to control cells while crocin decreased 10.5 % of LDHA activity in HeLa cells. These findings conclusively suggest that crocetin harbors more effective anticancer activity than crocin despite of low solubility. Further, it spurs the needs for investigation on biological activities of precursors of natural biological active compounds including terpenoids or flavonoids, for targeted production and treatment.