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Proposed cytotoxic mechanisms of the saffron carotenoids crocin and crocetin on cancer cell lines

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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.
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Keywords: ERO; LDHA; ROS; crocetin; crocin; crocine; crocétine

Document Type: Research Article

Affiliations: 1: 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. 2: Department of Physiology, Ajou University School of Medicine, Woncheon-dong, Yeongtong-gu, Suwon 443-721, Republic of Korea. 3: Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 373-1 Gwanhangno, Yusong-gu Taejon 305-701, Korea.

Publication date: January 1, 2014

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