title: Crocetin induces cytotoxicity and enhances vincristine-induced cancer cell death via p53-dependent and -independent mechanisms.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  Ccrocetin is a potential anticancer agent, which may be used as a chemotherapeutic drug or as a chemosensitizer for vincristine.
authors: Laboratory of Molecular and Translational Medicine, West China Second University Hospital, Sichuan University, Chengdu, China.
authors: Ying-jia
authors: YJ
authors: Zhong
authors: Fang
authors: F
authors: Shi
authors: Xue-lian
authors: XL
authors: Zheng
authors: Qiong
authors: Q
authors: Wang
authors: Lan
authors: L
authors: Yang
authors: Hong
authors: H
authors: Sun
authors: Fan
authors: F
authors: He
authors: Lin
authors: L
authors: Zhang
authors: Yong
authors: Y
authors: Lin
authors: Yong
authors: Y
authors: Qin
authors: Lin-chuan
authors: LC
authors: Liao
authors: Xia
authors: X
authors: Wang
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002338:Carotenoids / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004357:Drug Synergism; D005434:Flow Cytometry; D006801:Humans; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D014750:Vincristine / Q000494:pharmacology*; D014801:Vitamin A / Q000031:analogs & derivatives
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D016159:Tumor Suppressor Protein p53; C487773:trans-sodium crocetinate; D014801:Vitamin A; D002338:Carotenoids; D014750:Vincristine