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

作　　者：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 

机构地区：[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 [3]Department of Chemistry of Medicinal Natural Products, Key Laboratory of Drug Targeting and Novel Delivery System of the Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, China

出　　处：《Acta Pharmacologica Sinica》2011年第12期1529-1536,共8页中国药理学报（英文版）

基　　金：This study was supported in part by grants from the National Natural Science Foundation of China （No 30772539 and 30973403）, the Young Scientist Fund of Science ＆ Technology Department of Sichuan Province in China （2010JQ0012）, the Scientific Research Foundation for the Returned Overseas Chinese Scholar at the State Education Ministry of China, the Program for Changjiang Scholars and the Innovative Research Team in University （IRT0935）.

摘　　要：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.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.

关 键 词：CROCETIN VINCRISTINE cell cycle apoptosis P53 NEOPLASM 

分 类 号：Q55[生物学—生物化学] TQ463.54[化学工程—制药化工]