Crocetin induces cytotoxicity and enhances vincristine-induced cancer cell death via p53- dependent and ,independent mechanisms

Aim： To investigate the anticancer effect of crocetin, a major ingredient in saffron, and its underlying mechanisms. Methods： Cervical cancer cell line HeLa, non-small cell lung cancer cell line A549 and ovarian cancer cell line SKOV3 were treated with crocetin alone or in combination with vincristi...

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Bibliographic Details
Published in:Acta pharmacologica Sinica 2011-12, Vol.32 (12), p.1529-1536
Main Authors: Zhong, Ying-jia, Shi, Fang, Zheng, Xue-lian, Wang, Qiong, Yang, Lan, Sun, Hong, He, Fan, Zhang, Lin, Lin, Yong, Qin, Yong, Liao, Lin-chuan, Wang, Xia
Format: Article
Language:English
Subjects:
Annexins
Antineoplastic Agents, Phytogenic - pharmacology
Antitumor agents
Apoptosis
Apoptosis - drug effects
Breast cancer
Carotenoids - pharmacology
Caspase
Cell cycle
Cell death
Cell Line, Tumor
Cell proliferation
Cervical cancer
Cyclin-dependent kinase inhibitor p21
Cytotoxicity
Drug Synergism
Flow Cytometry
Humans
L-Lactate dehydrogenase
Non-small cell lung carcinoma
Original
Ovarian cancer
p53
p53 protein
propidium iodide
Tumor cell lines
Tumor Suppressor Protein p53 - metabolism
Vincristine
Vincristine - pharmacology
Western blotting
抗癌效果
机制
细胞死亡
细胞毒作用
西红花
诱导
长春新碱
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Summary:Aim： To investigate the anticancer effect of crocetin, a major ingredient in saffron, and its underlying mechanisms. Methods： Cervical cancer cell line HeLa, non-small cell lung cancer cell line A549 and ovarian cancer cell line SKOV3 were treated with crocetin alone or in combination with vincristine. Cell proliferation was examined using MTT assay. Cell cycle distribution and sub-G1 fraction were analyzed using flow cytometric analysis after propidium iodide staining. Apoptosis was detected using the Annexin V-FITC Apoptosis Detection Kit with flow cytometry. Cell death was measured based on the release of lactate dehydrogenase （LDH）. The expression levels of p53 and p21WAF1/cipl as well as caspase activation were examined using Western blot analysis. Results： Treatment of the 3 types of cancer cells with crocetin （60-240 μmol/L） for 48 h significantly inhibited their proliferation in a concentration-dependent manner. Crocetin （240 pmol/L） significantly induced cell cycle arrest through p53-dependent and -independent mechanisms accompanied with p21WAF1/Cipl induction. Crocetin （120-240μmol/L） caused cytotoxicity in the 3 types of cancer cells by enhancing apoptosis in a time-dependent manner. In the 3 types of cancer cells, crocetin （60 μmol/L） significantly enhanced the cytotoxicity induced by vincristine （1 μmol/L）. Furthermore, this synergistic effect was also detected in the vincristine-resistant breast cancer cell line MCF-7/VCR. Conclusion： Ccrocetin is a potential anticancer agent, which may be used as a chemotherapeutic drug or as a chemosensitizer for vincristine.
ISSN:1671-4083
1745-7254
DOI:10.1038/aps.2011.109