Proposed cytotoxic mechanisms of the saffron carotenoids crocin and crocetin on cancer cell lines.
We investigated the cytotoxic activities of crocin and crocetin, 2 major carotenoids isolated from the stigma of Crocus sativus (saffron), on 5 human cancer cell lines and proposed their possible anticancer mechanisms. Crocetin, a glycosylated carotenoid, showed approximately 5- to 18-fold higher cytotoxicity than crocin, a carboxylic carotenoid (IC50 of 0.16-0.61 mmol/L for crocetin vs. 2.0-5.5 mmol/L for crocin). This suggests that structural differences account for the different efficacies between them. Fluorescence-activated cell sorting (FACS) analysis showed that crocetin induced a significant level of cellular reactive oxygen species (ROS) in HeLa cells, whereas crocin did not. This ROS induction supported the cytotoxicity of crocetin, but not of crocin. A significant activation of nuclear factor erythroid 2-related factor 2 (Nrf2) was observed in both HeLa cells treated with crocin and crocetin: a 3.0-fold increase by 1 mmol/L crocetin and a 1.6-fold increase by 0.8 mmol/L crocin compared to the control. Furthermore, both crocetin and crocin reduced the protein expression of lactate dehydrogenase A (LDHA), one of the targets for chemoprevention in cancer cells, by 34.2% and 10.5%, respectively, compared to the control in HeLa cells. These findings suggest that crocetin and crocin have different mechanisms for their observed cytotoxicity in cancer cell lines.
a Department of Molecular Science and Technology and Department of Applied Chemistry and Biological Engineering, Ajou University, Woncheon-dong, Yeongtong-gu, Suwon 443-749, Republic of Korea.
Se Hyeuk
SH
Kim
Jung Min
JM
Lee
Sun Chang
SC
Kim
Chan Bae
CB
Park
Pyung Cheon
PC
Lee
D002338:Carotenoids / Q000494:pharmacology*; D045744:Cell Line, Tumor; D027622:Crocus / Q000737:chemistry*; D003603:Cytotoxins / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D000080864:Lactate Dehydrogenase 5; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014801:Vitamin A / Q000031:analogs & derivatives
D003603:Cytotoxins; D007527:Isoenzymes; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D017382:Reactive Oxygen Species; C487773:trans-sodium crocetinate; D014801:Vitamin A; D002338:Carotenoids; C029036:crocin; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5