Mitochondrially targeted wild-type p53 induces apoptosis in a solid human tumor xenograft model

Cell Cycle. 2008 Aug 15;7(16):2584-90. doi: 10.4161/cc.7.16.6070. Epub 2008 Aug 7.

Abstract

Classic but also novel roles of p53 are becoming increasingly well characterized. We previously showed that ex vivo retroviral transfer of mitochondrially targeted wild type p53 (mitop53) in the Emu-myc mouse lymphoma model efficiently induces tumor cell killing in vivo. In an effort to further explore the therapeutic potential of mitop53 for its pro-apoptotic effect in solid tumors, we generated replication-deficient recombinant human Adenovirus type 5 vectors. We show here that adenoviral delivery of mitop53 by intratumoral injection into HCT116 human colon carcinoma xenograft tumors in nude mice is surprisingly effective, resulting in tumor cell death of comparable potency to conventional p53. These apoptotic effects in vivo were confirmed by Ad5-mitop53 mediated cell death of HCT116 cells in culture. Together, these data provide encouragement to further explore the potential for novel mitop53 proteins in cancer therapy to execute the shortest known circuitry of p53 death signaling.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenoviridae
  • Animals
  • Apoptosis*
  • Cell Line, Tumor
  • Colonic Neoplasms / therapy*
  • Gene Transfer Techniques
  • Genetic Therapy
  • Humans
  • Mice
  • Mice, Nude
  • Mitochondria / metabolism*
  • Tumor Suppressor Protein p53 / genetics*
  • Xenograft Model Antitumor Assays

Substances

  • Tumor Suppressor Protein p53