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SHR Neuro Krebs Kardio Lipid Stoffw Microb
Kargl, J; Haybaeck, J; Stančić, A; Andersen, L; Marsche, G; Heinemann, A; Schicho, R.
O-1602, an atypical cannabinoid, inhibits tumor growth in colitis-associated colon cancer through multiple mechanisms.
J Mol Med (Berl). 2013; 91(4):449-458
Doi: 10.1007/s00109-012-0957-1
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- Führende Autor*innen der Med Uni Graz
- Kargl Julia
- Schicho Rudolf
- Co-Autor*innen der Med Uni Graz
- Haybäck Johannes
- Heinemann Akos
- Jacan Angela
- Marsche Gunther
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- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Antineoplastic Agents, Phytogenic - administration & dosage
- Apoptosis - drug effects
- Cell Line, Tumor -
- Cell Proliferation - drug effects
- Cell Survival - drug effects
- Colitis - complications
- Colonic Neoplasms - drug therapy
- Cyclohexanes - administration & dosage
- Disease Models, Animal -
- HT29 Cells -
- Humans -
- Male -
- Mice -
- Resorcinols - administration & dosage
- STAT3 Transcription Factor - metabolism
- Transcription Factor RelA - metabolism
- Tumor Burden - drug effects
- Tumor Necrosis Factor-alpha - metabolism
- Find related publications in this database (Keywords)
- Atypical cannabinoid
- Colitis-associated colon cancer
- Apoptosis
- Protumorigenic