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Crocin Inhibits Cell Proliferation and Enhances Cisplatin and Pemetrexed Chemosensitivity in Lung Cancer Cells

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Crocin Inhibits Cell Proliferation and Enhances Cisplatin and Pemetrexed Chemosensitivity in Lung Cancer Cells

Shuangshuang Chen et al. Transl Lung Cancer Res.

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.

Keywords: Crocin; cisplatin; lung adenocarcinoma; pemetrexed.

Conflict of interest statement

Conflicts of Interest: The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Crocin inhibited the proliferation of A549 and SPC-A1 cells in a concentration-dependent manner. (A) The growth of A549 cells was significantly inhibited after crocin treatment. The inhibition rate was significantly higher in the 48 h group compared to those in 24 h group; (B) the growth of SPC-A1 cells was significantly decreased after crocin treatment. The inhibition rate was significantly higher in the 48 h group compared to those in 24 h group. *, P<0.05; **, P<0.01; 24 h vs. 48 h.
Figure 2
Figure 2
Crocin induced apoptosis in A549 and SPC-A1 cells. Crocin significantly induced apoptosis in SPC-A1 cells after 48 h treatment in a dose-dependent pattern as analyzed by flow cytometry. *, P<0.05; **, P<0.01; treatment group vs. control group.
Figure 3
Figure 3
Crocin induced cell cycle arrest at G0/G1 phase. A549 (A) or SPC-A1 (B) cells were treated with crocin at the indicated concentrations for 48 h. Cell cycle distribution was analyzed by flow cytometry. *, P<0.05; **, P<0.01; treatment group vs. control group.
Figure 4
Figure 4
Crocin altered the gene expression of p53, Bax, and Bcl-2 in both A549 (A and B) and SPC-A1 (C and D) cells. mRNA levels of p53, Bax, and Bcl-2 were analyzed by RT-PCR. Relative mRNA level was normalized to β-actin mRNA level. *, P<0.05; **, P<0.01; treatment group vs. control group.
Figure 5
Figure 5
Crocin sensitized A549 and SPC-A1 cells to cisplatin and pemetrexed. The inhibitory effect of crocin (C) in combination with cisplatin (DDP) or pemetrexed (PMX). *, P<0.05, crocin vs. DDP+C; #, P<0.05, crocin vs. PMX+C.

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