Therapeutic molecular targeting of 15-lipoxygenase-1 in colon cancer

Mol Ther. 2008 May;16(5):886-92. doi: 10.1038/mt.2008.44. Epub 2008 Mar 18.


Molecular targeting for apoptosis induction is being developed for better treatment of cancer. Downregulation of 15-lipoxygenase-1 (15-LOX-1) is linked to colorectal tumorigenesis. Re-expression of 15-LOX-1 in cancer cells by pharmaceutical agents induces apoptosis. Antitumorigenic agents can also induce apoptosis via other molecular targets. Whether restoring 15-LOX-1 expression in cancer cells is therapeutically sufficient to inhibit colonic tumorigenesis remains unknown. We tested this question using an adenoviral delivery system to express 15-LOX-1 in in vitro and in vivo models of colon cancer. We found that (i) the adenoviral vector 5/3 fiber modification enhanced 15-LOX-1 gene transduction in various colorectal cancer cell lines, (ii) the adenoviral vector delivery restored 15-LOX-1 expression and enzymatic activity to therapeutic levels in colon cancer cell lines, and (iii) 15-LOX-1 expression downregulated the expression of the antiapoptotic proteins X-linked inhibitor of apoptosis protein (XIAP) and BcL-XL, activated caspase-3, triggered apoptosis, and inhibited cancer cell survival in vitro and the growth of colon cancer xenografts in vivo. Thus, selective molecular targeting of 15-LOX-1 expression is sufficient to re-establish apoptosis in colon cancer cells and inhibit tumorigenesis. These data provide the rationale for further development of therapeutic strategies to target 15-LOX-1 molecularly for treating colonic tumorigenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Antineoplastic Agents / pharmacology
  • Apoptosis
  • Arachidonate 15-Lipoxygenase / genetics*
  • Arachidonate 15-Lipoxygenase / metabolism*
  • Caspase 3 / metabolism
  • Colonic Neoplasms / enzymology*
  • Colonic Neoplasms / genetics*
  • Gene Expression Regulation, Neoplastic*
  • Gene Transfer Techniques
  • Genetic Therapy / methods*
  • Humans
  • Mice
  • Neoplasm Transplantation
  • X-Linked Inhibitor of Apoptosis Protein / metabolism
  • bcl-X Protein / metabolism


  • Antineoplastic Agents
  • X-Linked Inhibitor of Apoptosis Protein
  • XIAP protein, human
  • bcl-X Protein
  • Arachidonate 15-Lipoxygenase
  • Caspase 3