| Nucleoside transport inhibition is a novel stragery established for cancer chemotherapy in this laboratory. Investigations indicated that nucleoside transport inhibitors(NTI) could play a role as biochemical modulators to potentiate the cytotoxicity of several antitumor drugs and reverse drug resistance in tumor cells. In this research, nucleoside transport inhibition assay was first applied to direct the isolation of micro-organism products. The antitumor effects and mechanisms of 6011W-A, were investigated. Moreover, emodin as a plant-derived NTI was found to reverse drug resistance in tumor cells. Results are summarized as follows:1) Under the direction of nucleoside transport inhibition assay, 6011W-A, B and C were isolated from the fermentation broth of Streptoverticillium sp. 6011W. The structure of those compounds were elucidated as cinnamamide, N-(tetrahydro-2-oxo-3-thienyl)-acetamide, benzamide based on their physical-chemical properties and spectral data. They showed inhibitory effect on nucleoside transport with IC50 values of 30.4uM, 97.2uM and 85.4uM.2) 601 lW-A(cinnamamide) was found to be a low cytotoxic compound. With MTT assay, it inhibited the growth of several human rumor cell lines with IC50 values at the range of 1- 2 mM.At tolerable dosage levels, cinnamamide exhibited remarkable growth inhibition on transplanted tumors including colon carcinoma 26, hepatoma 22 and Lewis lung carcinoma in mice. It also reduced the number of lung lesions in experimental and spontaneous tumor metastasis...
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