Novel Cdk Inhibitor Xylocydine Shown to be Effective in Inducing Apoptosis in Hepatocellular Carcinoma Cells
Researchers in Seoul, Korea have discovered that a novel Cdk inhibitor, xylocydine, is an effective inducer of apoptosis in hepatocellular carcinoma (HCC) cells in vitro and in vivo. The study, published in Cancer Letters, demonstrates that xylocydine selectively down-regulates the activity of Cdk1 and Cdk2, leading to significant cell growth inhibition in HCC cells. Furthermore, the study found that xylocydine strongly inhibits the activity of Cdk7 and Cdk9, leading to apoptotic cell death in xylocydine-induced HCC cells.
Key Takeaways:
- Xylocydine, a novel Cdk inhibitor, was shown to be effective in inducing apoptosis in HCC cells in vitro and in vivo.
- The study demonstrated that xylocydine selectively down-regulates the activity of Cdk1 and Cdk2, leading to significant cell growth inhibition in HCC cells.
- Xylocydine also strongly inhibits the activity of Cdk7 and Cdk9, leading to apoptotic cell death in xylocydine-induced HCC cells.
- The study found that the effects of xylocydine on apoptosis were concomitant with changes in the levels of anti-apoptotic proteins, Bcl-2, XIAP, and survivin, which were markedly down-regulated, and pro-apoptotic molecules, p53 and Bax, which were elevated in HCC cells after treatment with xylocydine.
- The up-regulated level of p53 was associated with increased stability of the protein, as levels of Ser15 and Ser392 phosphorylated p53 were similarly elevated in the inhibitor-treated cells.
- The researchers demonstrated that xylocydine can effectively suppress the growth of HCC xenografts in Balb/C-nude mice by preferentially inducing apoptosis in the xenografts.
Statistics:
- The study used a concentration of 50muM of xylocydine to demonstrate its effects on HCC cells.
- The study found that the levels of anti-apoptotic proteins, Bcl-2, XIAP, and survivin, were markedly down-regulated in HCC cells after treatment with xylocydine.
- The levels of pro-apoptotic molecules, p53 and Bax, were elevated in HCC cells after treatment with xylocydine.
- The study demonstrated that the up-regulated level of p53 was associated with increased stability of the protein, as levels of Ser15 and Ser392 phosphorylated p53 were similarly elevated in the inhibitor-treated cells.
Sources:
- Cho, S.J., et al. (2010). Xylocydine, a novel Cdk inhibitor, is an effective inducer of apoptosis in hepatocellular carcinoma cells in vitro and in vivo. Cancer Letters, 287(2), 196-206.
- Seoul National University, Institute for Pharmaceutical Sciences.
- Cancer Weekly editors. (2010). Novel Cdk Inhibitor Xylocydine Shown to be Effective in Inducing Apoptosis in Hepatocellular Carcinoma Cells. Cancer Weekly.