Axl receptor tyrosine kinase is a novel target of apigenin for the inhibition of cell proliferation

Title
Axl receptor tyrosine kinase is a novel target of apigenin for the inhibition of cell proliferation
Author(s)
이추희김경찬[김경찬]최은하
Keywords
MYELOID-LEUKEMIA CELLS; HUMAN LUNG-CANCER; ACQUIRED-RESISTANCE; THERAPEUTIC TARGET; GROWTH ARREST; CYCLE ARREST; TUMOR-GROWTH; EXPRESSION; CARCINOMA; EGFR
Issue Date
201408
Publisher
SPANDIDOS PUBL LTD
Citation
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE, v.34, no.2, pp.592 - 598
Abstract
The Axl receptor tyrosine kinase (RTK), along with Tyro 3 and Mer, belongs to the TAM subfamily that promotes survival, stimulates proliferation and/or inhibits apoptosis. In various types of human cancer, including breast, lung and prostate cancer, Axl expression is increased and correlates with an advanced clinical stage. In this study, we examined whether apigenin has an effect on Axl expression, which in turn can affect cell proliferation. The treatment of the non-small cell lung cancer (NSCLC) cells, A549 and H460, with apigenin decreased Axl mRNA and protein expression in a dose-dependent manner. Axl promoter activity was also inhibited by apigenin, indicating that apigenin suppressed Axl expression at the transcriptional level. Upon treatment with apigenin, the viability of both the A549 and H460 cells was gradually decreased and the anti-proliferative effects were further confirmed by the dose-dependent decrease in the clonogenic ability of the apigenin-treated cells. Subsequently, we found that the viability and clonogenic ability of the cells treated with apigenin was less or more affected by transfection of the cells with a Axl-expressing plasmid or Axl targeting siRNA, compared to transfection with the empty vector or control siRNA, respectively. In addition, apigenin increased the expression of p21, a cyclin-dependent kinase inhibitor, but reduced the expression of X-linked inhibitor of apoptosis protein (XIAP). These cell cycle arrest and pro-apoptotic effects of apigenin were also attenuated or augmented by the up- or downregulation of Axl expression, respectively, which suggests that Axl is a novel target of apigenin through which it exerts its inhibitory effects on cell proliferation. Taken together, our data indicate that apigenin downregulates Axl expression, which subsequently results in the inhibition of NSCLC cell proliferation through the increase and decrease of p21 and XIAP expression, respectively.
URI
http://hdl.handle.net/YU.REPOSITORY/31192http://dx.doi.org/10.3892/ijmm.2014.1804
ISSN
1107-3756
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의과대학 > 생화학.분자생물학교실 > Articles
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