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有读书笔记Psoralidin, an Herbal Molecule, Inhibits Phosphatidylinositol 3-Kinase-Mediated Akt Signaling in Androgen-Independent Prostate Cancer Cells

leeallanchina 添加于 2010-1-5 02:00 | 2921 次阅读 | 0 个评论

  •  作 者

    Kumar R, Srinivasan S, Koduru S, Pahari P, Rohr J, Kyprianou N, Damodaran C

  •  摘 要

    The protein kinase Akt plays an important role in cell proliferation and survival in many cancers, including prostate cancer. Due to its kinase activity, it serves as a molecular conduit for inhibiting apoptosis and promoting angiogenesis in most cell types. In most of the prostate tumors, Akt signaling is constitutively activated due to the deletion or mutation of the tumor suppressor PTEN, which negatively regulates phosphatidylinositol 3-kinase through lipid phosphatase activity. Recently, we identified a natural compound, psoralidin, which inhibits Akt phosphorylation, and its consequent activation in androgen-independent prostate cancer (AIPC) cells. Furthermore, ectopic expression of Akt renders AIPC cells resistant to chemotherapy; however, psoralidin overcomes Akt-mediated resistance and induces apoptosis in AIPC cells. While dissecting the molecular events, both upstream and downstream of Akt, we found that psoralidin inhibits phosphatidylinositol 3-kinase activation and transcriptionally represses the activation of nuclear factor-B and its target genes (Bcl-2, Survivin, and Bcl-xL, etc.), which results in the inhibition of cell viability and induction of apoptosis in PC-3 and DU-145 cells. Interestingly, psoralidin selectively targets cancer cells without causing any toxicity to normal prostate epithelial cells. In vivo xenograft assays substantiate these in vitro findings and show that psoralidin inhibits prostate tumor growth in nude mice. Our findings are of therapeutic significance in the management of prostate cancer patients with advanced or metastatic disease, as they provide new directions for the development of a phytochemical-based platform for prevention and treatment strategies for AIPC.

  •  详细资料

    • 文献种类: Journal Article
    • 期刊名称: Cancer Prevention Research
    • 期刊缩写: Cancer Prevention Research
    • 期卷页: 2009年  第2卷 第3期 234-243页
    • ISBN: 1940-6207

  • 学科领域 生物医药 » 中医中药学

  •  标 签

    Akt  signaling  •  apoptosis  natural  compound 

  • 相关链接 DOI URL 

  •  leeallanchina 的文献笔记  订阅

    补骨脂次素抑制雄激素非依赖性前列腺癌细胞的磷脂酰肌醇3激酶介导的 AKT信号传导途径

    补骨脂次素抑制雄激素非依赖性前列腺癌细胞的磷脂酰肌醇3激酶介导的 AKT信号传导途径，，最后引起凋亡，中医上认为补骨脂为温补脾肾的要药，具有补肾壮阳，固精缩尿，温脾止泻等作用。主治肾虚腰膝冷痛，阳痿，小便频数，遗精，脾肾阳虚，泄泻便搪，或五更黎明时泄泻等症。那是否可开发为抗前列腺癌的药物呢？

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