O-1602, an atypical cannabinoid, inhibits tumor growth in colitis-associated colon cancer through multiple mechanisms

J Mol Med (Berl). 2013 Apr;91(4):449-58. doi: 10.1007/s00109-012-0957-1. Epub 2012 Sep 11.


Cannabinoids have antiinflammatory and antitumorigenic properties. Some cannabinoids, such as O-1602, have no or only little affinity to classical cannabinoid receptors but exert cannabinoid-like antiinflammatory effects during experimental colitis. Here, we investigated whether O-1602 shows antitumorigenic effects in colon cancer cells and whether it could reduce tumorigenesis in the colon in vivo. The colon cancer cell lines HT-29 and SW480 were used to study the effect of O-1602 on viability and apoptosis. The effect of O-1602 on tumor growth in vivo was studied in a colitis-associated colon cancer mouse model. O-1602 decreased viability and induced apoptosis in colon cancer cells in a concentration-dependent manner (0.1-10 μM). In the mouse model, treatment with O-1602 (3 mg/kg, i.p., 12×) reduced tumor area by 50 % and tumor incidence by 30 %. Histological scoring revealed a significant decrease in tumor load. In tumor tissue, O-1602 decreased levels of proliferating cell nuclear antigen (PCNA), activation of oncogenic transcription factors STAT3 and NFκB p65, and expression of TNF-α while levels for proapoptotic markers, such as p53 and BAX, increased. The in vivo effects of O-1602 on PCNA, BAX, and p53 were also observed in colon cancer cells. The data provide a novel insight into antitumorigenic mechanisms of atypical cannabinoids. O-1602 exerts antitumorigenic effects by targeting colon cancer cells as well as proinflammatory pathways known to promote colitis-associated tumorigenesis. Due to its lack of central sedation, O-1602 could be an interesting compound for the treatment of colon and possibly other cancers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / administration & dosage
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects
  • Cannabidiol / analogs & derivatives
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Colitis / complications*
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / etiology*
  • Cyclohexanes / administration & dosage
  • Cyclohexanes / pharmacology*
  • Disease Models, Animal
  • HT29 Cells
  • Humans
  • Male
  • Mice
  • Resorcinols / administration & dosage
  • Resorcinols / pharmacology*
  • STAT3 Transcription Factor / metabolism
  • Transcription Factor RelA / metabolism
  • Tumor Burden / drug effects
  • Tumor Necrosis Factor-alpha / metabolism


  • Antineoplastic Agents, Phytogenic
  • Cyclohexanes
  • Resorcinols
  • STAT3 Transcription Factor
  • Transcription Factor RelA
  • Tumor Necrosis Factor-alpha
  • Cannabidiol
  • O-1602 compound