Silybin has therapeutic efficacy against non-small cell lung cancer through targeting of Skp2
Silybin (SB), a natural flavonoid isolated from Silybum marianum, has been used to treat hepatic fibrosis in clinical settings and as a dietary supplement, because of its hepatoprotective potential. Numerous studies have shown that SB also exerts promising anticancer effects; however, the anticancer...
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| Main Authors: | , , , , , , , |
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| Format: | Book |
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Compuscript Ltd,
2022-08-01T00:00:00Z.
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| Summary: | Silybin (SB), a natural flavonoid isolated from Silybum marianum, has been used to treat hepatic fibrosis in clinical settings and as a dietary supplement, because of its hepatoprotective potential. Numerous studies have shown that SB also exerts promising anticancer effects; however, the anticancer targets of SB and the underlying mechanism were unclear. Herein, we found that SB significantly inhibited the proliferation of non-small cell lung cancer without causing cytotoxicity toward normal Beas-2B bronchial epithelial cells. Mechanistically, SB binds the F-box protein Skp2 and disrupts Skp1-Skp2 interaction, thereby decreasing Skp2 protein levels, inducing accumulation of Skp2 substrates, and leading to G1-phase cell-cycle arrest and the suppression of cell migration. In lung orthotopic xenografts, SB also significantly decreased Skp2 expression and increased p27/Kip1 protein levels. SB administration inhibited tumor growth and metastasis in lung tissue, thus prolonging survival time in mice without causing obvious toxicity. Thus, SB is a potential Skp2-targeting agent that warrants further clinical investigation. |
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| Item Description: | 2737-7946 10.15212/AMM-2022-0011 |