Silibinin Activates p53-Caspase 2 Pathway and Causes Caspase-Mediated Cleavage of Cip1/p21 in Apoptosis Induction

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Recent research has shed light on the mechanisms involved in silibinin-induced apoptosis of RT4 cells, having intact p53. The study found that silibinin increased p53 protein level and activated caspase cascade, leading to apoptosis. The researchers also discovered a regulatory loop between p53 and caspase 2, where silibinin-caused p53 activation was mediated via ATM-Chk2 pathway, inducing caspase 2-mediated apoptosis. Additionally, silibinin caused rapid translocation of p53 and Bid into mitochondria, leading to increased permeabilization of mitochondrial membrane and cytochrome c release into the cytosol.

Key Takeaways:

  • Silibinin activates the p53-caspase 2 pathway and causes caspase-mediated cleavage of Cip1/p21 in apoptosis induction in bladder transitional-cell papilloma RT4 cells.
  • Silibinin increased p53 protein level and activated caspase cascade, leading to apoptosis.
  • Pifithrin-alpha, a p53 inhibitor, reversed silibinin-induced caspase activation and caspase 2-mediated apoptosis.
  • Caspase 2 inhibitor also reversed p53 phosphorylation, suggesting a bidirectional regulation between them.
  • Silibinin caused rapid translocation of p53 and Bid into mitochondria, leading to increased permeabilization of mitochondrial membrane and cytochrome c release into the cytosol.
  • JNK1/2 activation was observed as a connecting link for p53-mediated caspase 2 activation.
  • Silibinin-induced apoptosis was mediated, in part, via Cip1/p21 cleavage by caspase, which was reversed by Cip1/p21 siRNA.

Statistics:

  • 27(11) is the journal volume and issue in which the study was published.
  • 2269-80 is the page range of the published study.
  • 2006 is the publication year of the study.
  • Carcinogenesis is the journal in which the study was published.
  • 34 is the number of references cited in the study.

Sources:

  • Tyagi A, et al. (2006). Silibinin activates p53-caspase 2 pathway and causes caspase-mediated cleavage of Cip1/p21 in apoptosis induction in bladder transitional-cell papilloma RT4 cells: evidence for a regulatory loop between p53 and caspase 2. Carcinogenesis, 27(11), 2269-80.
  • Health & Medicine Week editors (2006). Silibinin Activates p53-Caspase 2 Pathway and Causes Caspase-Mediated Cleavage of Cip1/p21 in Apoptosis Induction. Health & Medicine Week, [online database]. Available from: https://www.newsrx.com/article/224605137.html
  • University of Colorado Health Sciences Center (2006). Contact A. Tyagi, University of Colorado Health Sciences Center Denver, Dept. of Pharmaceutical Sciences, School of Pharmacy, CO 80262 U.S.