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Basement membrane biosynthesis as a target to tumor therapy
M E Maragoudakis1, E Missirlis, M Sarmonika
1Department of Pharmacology, University of Patras Medical School, Greece.
Abstract:
Tricyclodecan-9-yl-xanthate (D609) was identified as an agent that caused selective killing of tumor cells by an unknown mechanism of action. We report an inhibition by D609 of basement membrane collagen biosynthesis in the chick chorioallantoic membrane system in vitro. In the same system in vivo D609 inhibits angiogenesis. Also treatment of rats bearing Walker 256 carcinoma with D609 results in a dose-dependent antitumor effect. These results indicate that basement membrane synthesis may be a target for developing anti-angiogenic compounds with antitumor properties.
Insights
Tricyclodecan-9-yl-xanthate (D609) selectively kills tumor cells by inhibiting collagen synthesis and angiogenesis. This compound shows a dose-dependent antitumor effect in rats, suggesting basement membrane synthesis as a target for novel anti-angiogenic cancer therapies.
Area of Science:
- Biochemistry
- Oncology
- Pharmacology
Background:
- Tricyclodecan-9-yl-xanthate (D609) demonstrates selective tumor cell killing via an unelucidated mechanism.
- Basement membrane collagen biosynthesis and angiogenesis are critical in tumor growth and metastasis.
Purpose of the Study:
- To investigate the mechanism of action of D609.
- To evaluate the anti-angiogenic and antitumor effects of D609.
Main Methods:
- In vitro studies using chick chorioallantoic membrane to assess collagen biosynthesis and angiogenesis inhibition.
- In vivo studies involving rats bearing Walker 256 carcinoma treated with D609.
Main Results:
- D609 significantly inhibited basement membrane collagen biosynthesis in vitro.
- D609 demonstrated anti-angiogenic activity in the chick chorioallantoic membrane model.
- D609 treatment resulted in a dose-dependent reduction in tumor size in rats with Walker 256 carcinoma.
Conclusions:
- D609's mechanism involves the inhibition of basement membrane collagen synthesis.
- D609 exhibits promising anti-angiogenic and antitumor properties.
- Targeting basement membrane synthesis represents a potential strategy for developing novel anti-angiogenic cancer therapeutics.