Background: FBXO32 is an E3 ubiquitin ligase that plays important roles in tumorigenesis and muscle atrophy. Results: c-Myc was found to be a target of FBXO32 for proteasomal degradation. Conclusion: FBXO32 targets Lys-326 of c-Myc to form polyubiquitin chains, resulting in inhibition of cell proliferation. Significance: FBXO32 may mediate c-Myc proteasomal degradation.
Aim: To investigate the effects and possible mechanisms of tanshinone II-A, an alcohol extract of the root of Salvia miltiorrhiza Bunge, on tumor invasion and metastasis of human colon carcinoma (CRC) cells. Methods: The effects of tanshinone II-A on invasion and metastasis of CRC cell lines HT29 and SW480 were evaluated by in vitro and in vivo assays. Western blotting was used to investigate possible molecular mechanisms of tanshinone II-A anti-cancer actions. Results: Tanshinone II-A inhibited migration and invasion of CRC cells in a dose-dependent manner. The inhibitory effect also depended on time, with the most significant effects observed at 72 h. Tanshinone II-A also significantly inhibited in vivo metastasis of colon carcinoma SW480 cells. It inhibited in vitro and in vivo invasion and metastasis of CRC cells by reducing levels of urokinase plasminogen activator (uPA) and matrix metalloproteinases (MMP)-2 and MMP-9, and by increasing levels of tissue inhibitor of matrix metalloproteinase protein (TIMP)-1 and TIMP-2. Tanshinone II-A was also shown to suppress the nuclear factor-kappaB (NF-κB) signal. Conclusion: Tanshinone II-A inhibited in vitro and in vivo invasion and metastasis of CRC cells. The effect resulted from changes in the levels of uPA, MMP-2, MMP-9, TIMP-1, and TIMP-2, and apparent inhibition of the NF-κB signal transduction pathway.
Materials and methods
Cell culture and materialsThe human colon carcinoma cell lines HT29 and SW480 were obtained from the American Type Culture Collection. HT29 cells were cultured in 1640 medium (Sigma-Aldrich), while SW480 cells were cultured in L-15 medium (Sigma-Aldrich). Media were supplemented with 10% fetal bovine serum (Atlanta Biologicals), and cells were cultured at 37 °C in 5% CO 2 .
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