Erianin Induces Apoptosis Of Colorectal Cancer Cells Via Activation Of Jnk Signaling Pathways
INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL MEDICINE(2019)
摘要
The current study aimed to investigate the anti-cancer activity of erianin on human colorectal carcinoma cell lines, exploring the underlying molecular mechanisms. After administration with erianin, inhibition of proliferation was quantitatively measured with colorimetric MTT assays. Morphologic changes were observed with DAPI staining. Flow cytometry analysis was conducted with Annexin-V-FITC/PI double staining, aiming to determine the effects of erianin on cell cycle and apoptosis levels. Western blotting was used to detect expression of cell cycle and apoptosis-related proteins after erianin treatment. Sp600125, a JNK signaling inhibitor, was used to confirm the regulatory effects of the anti-neoplastic activity of erianin. Results suggest that the proliferation of human colorectal cells could be significantly inhibited after 24 hours of treatment with erianin, in a dose-dependent manner. The IC50 value was 70.96 nM for SW620 and 106.52 nM for HCT116. DAPI staining showed typical morphologic changes of apoptosis after erianin treatment. With increased concentrations of erianin, the cell number at the G2/M phase was increased after 24 hours. Significant increases in the number of apoptotic cells were observed in SW620 cells via Annexin-V-FITC/PI double staining. Furthermore, erianin activated expression of p21 and p27 and suppressed expression of CDK1 and Cyclin B1, inducing cell cycle G2/M phase arrest. Apoptosis-related proteins (p53, Bax) were upregulated by erianin, while PARP and Bcl-2 proteins were downregulated. Phosphorylation levels of JNK increased, in a dose-dependent manner, after erianin treatment. A selective inhibitor of JNK, sp600125, weakened apoptosis levels of SW620 cells induced by erianin. Results suggest that erianin may play a role in proliferation and apoptosis of colorectal cancer cells by affecting JNK pathways, paving the road for further application of erianin in colorectal cancer therapy.
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关键词
Erianin, colorectal cancer, cell cycle and apoptosis, JNK signaling pathway
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