New plant-derived lead compounds against colorectal tumors

Many cancer deaths in industrialized countries are caused by colorectal carcinomas. Important charac-teristics of these cancers are high inherent resistence and low response to therapy. In advanced carci-nomas prognosis is bad. Investigations focussing on new drugs with alternative mechanisms of action are an important task to improve therapy and prognosis. For an effective search for new therapeutics the enormous structural diversity of secondary plant metabolites provides a rich resource. Different active plant compounds e.g. taxol, vinblastin, have gained importance as anticancer drugs. Thus, from close cooperation of pharmacognosy and cancer research in this project a trend-setting strategy to accelerated isolation of promising compounds against colorectal carcinomas is expected. The project focusses on the bioassay-guided isolation of cytostatic/cytotoxic compounds from Latin American plants such as Metaxya rostrata, Stachytarpheta jamaicensis, Verbena littoralis or Maranta arundinacea. For the provision of plant material the new facilities of the Univ. of Vienna in La Gamba, Costa Rica, are an indispensible incentive. Within the project, pharmacognostic research provides the identification of promising plants; by state-of- the-art methods for extraction and fractionation respective extracts and fractions will be obtained and active constituents isolated and their structures elucidated. In cancer research the isolated compounds will be analyzed for cytostatic and cytotoxic effects using colorectal tumor cells and transplanted tumors in a mouse model. Biological effects and the underlying cellular mechanisms in human colorectal tumor cells will be explored by analyzing cell cycle progression, apoptosis signaling and inhibition of histone deacetylases. The inhibition of these enzymes is a very recent approach in cancer treatment. Thus, the search for natural compounds with the respective activity may provide completely new cytostatic and cytotoxic lead structures. The results should identify candidate compounds for the chemotherapy of colorectal carcinomas and will provide the basis for large-scale isolation, further development of compounds in preclinical studies and production of semisynthetic derivatives. The project should contribute to an improvement in the treatment of advanced colorectal tumors, increased response and better prognosis.

Many cancer deaths in industrialized countries are caused by colorectal carcinomas. Important characteristics of these cancers are high inherent resistence and low response to therapy. In advanced carcinomas prognosis is bad. Investigations focussing on new drugs with alternative mechanisms of action are an important task to improve therapy and prognosis. For an effective search for new therapeutics the enormous structural diversity of secondary plant metabolites provides a rich resource. Different active plant compounds e.g. taxol, vinblastin, have gained importance as anticancer drugs. Thus, from close cooperation of pharmacognosy and cancer research in this project a trend-setting strategy to accelerated isolation of promising compounds against colorectal carcinomas is expected. The project focusses on the bioassay-guided isolation of cytostatic/cytotoxic compounds from Latin American plants such as Metaxya rostrata, Stachytarpheta jamaicensis, Verbena littoralis or Maranta arundinacea. For the provision of plant material the new facilities of the Univ. of Vienna in La Gamba, Costa Rica, are an indispensible incentive. Within the project, pharmacognostic research provides the identification of promising plants; by state-of- the-art methods for extraction and fractionation respective extracts and fractions will be obtained and active constituents isolated and their structures elucidated. In cancer research the isolated compounds will be analyzed for cytostatic and cytotoxic effects using colorectal tumor cells and transplanted tumors in a mouse model. Biological effects and the underlying cellular mechanisms in human colorectal tumor cells will be explored by analyzing cell cycle progression, apoptosis signaling and inhibition of histone deacetylases. The inhibition of these enzymes is a very recent approach in cancer treatment. Thus, the search for natural compounds with the respective activity may provide completely new cytostatic and cytotoxic lead structures. The results should identify candidate compounds for the chemotherapy of colorectal carcinomas and will provide the basis for large-scale isolation, further development of compounds in preclinical studies and production of semisynthetic derivatives. The project should contribute to an improvement in the treatment of advanced colorectal tumors, increased response and better prognosis.