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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.
The Journal of Pharmacology and Experimental Therapeutics
|February 1, 1990
Summary
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.