title: Crocin inhibits cell proliferation and enhances cisplatin and pemetrexed chemosensitivity in lung cancer cells.
abstract: BACKGROUND
  Crocin is the major constituent of saffron, a naturally derived Chinese medicine obtained from the dried stigma of the Crocus sativus flower. It has a variety of pharmacological effects, including anti-oxidative, immunity enhancement, and anti-tumorigenic properties; however, the molecular mechanisms underlying these effects remain unknown.
  
  
  METHODS
  To investigate the effects of crocin on proliferation and apoptosis of lung adenocarcinoma cells, lung adenocarcinoma cell lines, A549 and SPC-A1, were treated with crocin at different dosages. Cell morphological changes were observed by light microscopy. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed to detect the inhibitory effect of crocin on cell proliferation and sensitivity to chemotherapeutic drugs. Flow cytometry was used to characterize cell apoptosis and cell cycle profiles. Reverse transcription-polymerase chain reaction was used to detect mRNA levels of apoptosis-related genes.
  
  
  RESULTS
  Crocin inhibited cell proliferation and induced apoptosis in A549 and SPC-A1 cells in a concentration-dependent manner, accompanied with an increase of G0/G1 arrest. Crocin significantly increased the mRNA levels of both p53 and B-cell lymphoma 2-associated X protein (Bax), while decreasing B-cell lymphoma 2 (Bcl-2) mRNA expressions. In addition, crocin combined with either cisplatin or pemetrexed showed additive effects on cell proliferation in two lung cancer cell lines.
  
  
  CONCLUSIONS
  Crocin significantly suppressed the proliferation of human lung adenocarcinoma cells and enhanced the chemo sensitivity of these cells to both cisplatin and pemetrexed. The actions of molecular mechanism could be through the induction of cell cycle arrest and apoptosis by p53 and Bax up-regulation but Bcl-2 down-regulation.
authors.affiliation: 1 Department of Medical Oncology, Jinling Hospital, Nanjing University of Chinese Medicine, Nanjing 210002, China ; 2 Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China ; 3 Mingde Hospital affiliated with Nanjing Medical University, Nanjing 210000, China ; 4 Changzhou TCM Hospital, Changzhou 213000, China ; 5 Shanghai Medical College of Fudan University, Shanghai 200433, China ; 6 Weinberg college of Arts and Sciences at Northwestern University, Evanston, Illinois 60204, USA ; 7 Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA ; 8 Department of Respiratory Medicine, Jinling Hospital, Nanjing 210002, China.
authors.forename: Shuangshuang
authors.initials: S
authors.lastname: Chen
authors.affiliation: 1 Department of Medical Oncology, Jinling Hospital, Nanjing University of Chinese Medicine, Nanjing 210002, China ; 2 Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China ; 3 Mingde Hospital affiliated with Nanjing Medical University, Nanjing 210000, China ; 4 Changzhou TCM Hospital, Changzhou 213000, China ; 5 Shanghai Medical College of Fudan University, Shanghai 200433, China ; 6 Weinberg college of Arts and Sciences at Northwestern University, Evanston, Illinois 60204, USA ; 7 Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA ; 8 Department of Respiratory Medicine, Jinling Hospital, Nanjing 210002, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Zhao
authors.affiliation: 1 Department of Medical Oncology, Jinling Hospital, Nanjing University of Chinese Medicine, Nanjing 210002, China ; 2 Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China ; 3 Mingde Hospital affiliated with Nanjing Medical University, Nanjing 210000, China ; 4 Changzhou TCM Hospital, Changzhou 213000, China ; 5 Shanghai Medical College of Fudan University, Shanghai 200433, China ; 6 Weinberg college of Arts and Sciences at Northwestern University, Evanston, Illinois 60204, USA ; 7 Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA ; 8 Department of Respiratory Medicine, Jinling Hospital, Nanjing 210002, China.
authors.forename: Xinxing
authors.initials: X
authors.lastname: Wang
authors.affiliation: 1 Department of Medical Oncology, Jinling Hospital, Nanjing University of Chinese Medicine, Nanjing 210002, China ; 2 Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China ; 3 Mingde Hospital affiliated with Nanjing Medical University, Nanjing 210000, China ; 4 Changzhou TCM Hospital, Changzhou 213000, China ; 5 Shanghai Medical College of Fudan University, Shanghai 200433, China ; 6 Weinberg college of Arts and Sciences at Northwestern University, Evanston, Illinois 60204, USA ; 7 Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA ; 8 Department of Respiratory Medicine, Jinling Hospital, Nanjing 210002, China.
authors.forename: Luo
authors.initials: L
authors.lastname: Zhang
authors.affiliation: 1 Department of Medical Oncology, Jinling Hospital, Nanjing University of Chinese Medicine, Nanjing 210002, China ; 2 Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China ; 3 Mingde Hospital affiliated with Nanjing Medical University, Nanjing 210000, China ; 4 Changzhou TCM Hospital, Changzhou 213000, China ; 5 Shanghai Medical College of Fudan University, Shanghai 200433, China ; 6 Weinberg college of Arts and Sciences at Northwestern University, Evanston, Illinois 60204, USA ; 7 Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA ; 8 Department of Respiratory Medicine, Jinling Hospital, Nanjing 210002, China.
authors.forename: Enze
authors.initials: E
authors.lastname: Jiang
authors.affiliation: 1 Department of Medical Oncology, Jinling Hospital, Nanjing University of Chinese Medicine, Nanjing 210002, China ; 2 Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China ; 3 Mingde Hospital affiliated with Nanjing Medical University, Nanjing 210000, China ; 4 Changzhou TCM Hospital, Changzhou 213000, China ; 5 Shanghai Medical College of Fudan University, Shanghai 200433, China ; 6 Weinberg college of Arts and Sciences at Northwestern University, Evanston, Illinois 60204, USA ; 7 Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA ; 8 Department of Respiratory Medicine, Jinling Hospital, Nanjing 210002, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Gu
authors.affiliation: 1 Department of Medical Oncology, Jinling Hospital, Nanjing University of Chinese Medicine, Nanjing 210002, China ; 2 Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China ; 3 Mingde Hospital affiliated with Nanjing Medical University, Nanjing 210000, China ; 4 Changzhou TCM Hospital, Changzhou 213000, China ; 5 Shanghai Medical College of Fudan University, Shanghai 200433, China ; 6 Weinberg college of Arts and Sciences at Northwestern University, Evanston, Illinois 60204, USA ; 7 Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA ; 8 Department of Respiratory Medicine, Jinling Hospital, Nanjing 210002, China.
authors.forename: Anna Junjie
authors.initials: AJ
authors.lastname: Shangguan
authors.affiliation: 1 Department of Medical Oncology, Jinling Hospital, Nanjing University of Chinese Medicine, Nanjing 210002, China ; 2 Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China ; 3 Mingde Hospital affiliated with Nanjing Medical University, Nanjing 210000, China ; 4 Changzhou TCM Hospital, Changzhou 213000, China ; 5 Shanghai Medical College of Fudan University, Shanghai 200433, China ; 6 Weinberg college of Arts and Sciences at Northwestern University, Evanston, Illinois 60204, USA ; 7 Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA ; 8 Department of Respiratory Medicine, Jinling Hospital, Nanjing 210002, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhao
authors.affiliation: 1 Department of Medical Oncology, Jinling Hospital, Nanjing University of Chinese Medicine, Nanjing 210002, China ; 2 Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China ; 3 Mingde Hospital affiliated with Nanjing Medical University, Nanjing 210000, China ; 4 Changzhou TCM Hospital, Changzhou 213000, China ; 5 Shanghai Medical College of Fudan University, Shanghai 200433, China ; 6 Weinberg college of Arts and Sciences at Northwestern University, Evanston, Illinois 60204, USA ; 7 Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA ; 8 Department of Respiratory Medicine, Jinling Hospital, Nanjing 210002, China.
authors.forename: Tangfeng
authors.initials: T
authors.lastname: Lv
authors.affiliation: 1 Department of Medical Oncology, Jinling Hospital, Nanjing University of Chinese Medicine, Nanjing 210002, China ; 2 Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China ; 3 Mingde Hospital affiliated with Nanjing Medical University, Nanjing 210000, China ; 4 Changzhou TCM Hospital, Changzhou 213000, China ; 5 Shanghai Medical College of Fudan University, Shanghai 200433, China ; 6 Weinberg college of Arts and Sciences at Northwestern University, Evanston, Illinois 60204, USA ; 7 Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA ; 8 Department of Respiratory Medicine, Jinling Hospital, Nanjing 210002, China.
authors.forename: Zhenghong
authors.initials: Z
authors.lastname: Yu
keywords: Crocin; cisplatin; lung adenocarcinoma; pemetrexed