Journal of Molecular Medicine

, Volume 91, Issue 4, pp 449–458 | Cite as

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

  • Julia Kargl
  • Johannes Haybaeck
  • Angela Stančić
  • Liisa Andersen
  • Gunther Marsche
  • Akos Heinemann
  • Rudolf Schicho
Original Article

Abstract

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.

Keywords

Atypical cannabinoid Colitis-associated colon cancer Apoptosis Protumorigenic 

Supplementary material

109_2012_957_MOESM1_ESM.pdf (245 kb)
ESM 1(PDF 244 kb)

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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Julia Kargl
    • 1
  • Johannes Haybaeck
    • 2
  • Angela Stančić
    • 1
  • Liisa Andersen
    • 1
  • Gunther Marsche
    • 1
  • Akos Heinemann
    • 1
  • Rudolf Schicho
    • 1
  1. 1.Institute of Experimental and Clinical PharmacologyMedical University of GrazGrazAustria
  2. 2.Institute of PathologyMedical University of GrazGrazAustria

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