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Food Chem Toxicol. 2014 May;67:187-92. doi: 10.1016/j.fct.2014.02.035. Epub 2014 Mar 5.

Sinapine as an active compound for inhibiting the proliferation of Caco-2 cells via downregulation of P-glycoprotein.

Author information

1
School of Pharmacy, Xi'an Jiaotong University, Xi'an, China.
2
Center for Translational Medicine, The First Affiliated Hospital, College of Medicine, Xi'an Jiaotong University, Xi'an 710061, China.
3
School of Pharmacy, Xi'an Jiaotong University, Xi'an, China. Electronic address: taozhang@mail.xjtu.edu.cn.

Abstract

Sinapine, an alkaloid from seeds of the cruciferous species, shows favorable biological activities such as antioxidant and radio-protective activities. However, the inhibitory effect of sinapine on tumors, and the molecular mechanisms have not been completely understood thus far. In this study, we determined anti-proliferative effects of sinapine. We examined the anti-tumor effects of the combination of sinapine and doxorubicin. The results of the MTT assay and apoptosis showed that sinapine increased the sensitivity of Caco-2 cells to doxorubicin in a dose-dependent manner, whereas no or less effect was observed in the cells treated with doxorubicin alone. The combination of sinapine and doxorubicin had a synergistic effect and increased the cytotoxicity of doxorubicin against Caco-2 cells. Doxorubicin accumulation assay showed that sinapine increased the intracellular accumulation of doxorubicin in dose-dependent manner. Immunoblotting and QT-PCR analysis showed that sinapine suppressed P-glycoprotein (P-gp) expression via ubiquitination. A significant correlation was observed between the expression of p-ERK1/2 and P-gp. These results indicated that sinapine played an important role in the down-regulation of P-gp expression through suppression of FGFR4-FRS2α-ERK1/2 signaling pathway. To our knowledge, this is the first study to show that sinapine can be used as an effective natural compound for chemo-resistance.

KEYWORDS:

Caco-2; ERK1/2; FGFR4; P-glycoprotein; Sinapine; p-FRS2α

PMID:
24607798
DOI:
10.1016/j.fct.2014.02.035
[Indexed for MEDLINE]

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