Abstract Title:

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

Abstract Source:

Acta Pharmacol Sin. 2011 Oct 10. Epub 2011 Oct 10. PMID: 21986580

Abstract Author(s):

Ying-Jia Zhong, Fang Shi, Xue-Lian Zheng, Qiong Wang, Lan Yang, Hong Sun, Fan He, Lin Zhang, Yong Lin, Yong Qin, Lin-Chuan Liao, Xia Wang

Article Affiliation:

1] Laboratory of Molecular and Translational Medicine, Key Laboratory of Obstetric, Gynecologic and Pediatric Diseases and Birth Defects of the Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, China [2] Department of Forensic Analytical Toxicology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu 610041, China.

Abstract:

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-G(1) 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 p21(WAF1/Cip1) 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 μmol/L) significantly induced cell cycle arrest through p53-dependent and -independent mechanisms accompanied with p21(WAF1/Cip1) induction. Crocetin (120-240 μmol/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.

Study Type : In Vitro Study
Additional Links
Pharmacological Actions : Chemosensitizer : CK(1124) : AC(1199)

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