In view of the clear evidence that urokinase typeplasminogen activator (uPA) plays an important role in the processes of tumorcell metastasis, aortic aneurysm, and multiple sclerosis, it has become atarget of choice for pharmacological intervention. Thegoal of this study thus, was to determine the presence of inhibitors of uPA inplants known traditionally for their anti-tumor properties. Crudemethanol extracts were prepared from the leaves of plants (14) collected fromthe Subtropical Dry Forest (Guanica)in Puerto Rico, and tested for the presence of inhibitors of uPAusing Fibrin Plate Assay. The extracts that tested positive (6) were thenpartitioned with petroleum ether , chloroform , ethyl acetate and n-butanol ,in a serial manner. The resulting partitions were then tested using again thefibrin plate assay. Extract partitions from leaves of Croton lucidus (C. lucidus) showed the presence of astrong uPA inhibitory activity. Serial dilutions of these C. lucidus partitions were performed to determine the uPAinhibition IC50 values. The chloroform partition showedthe lowest IC50 value (3.52 �g/mL) and hence the most potent uPAinhibitor. Further investigations revealed that the crude methanol extract andits chloroform and n-butanol partitions did not inhibit significantly the closelyrelated proteases such as the tissue type plasminogen activator (tPA) andplasmin, indicating their selectivity for uPA, and hence superior potential formedicinal use with fewer side effects. In a further evaluation of theirtherapeutic potential for prevention of cancer metastasis, the C. lucidusextractsdisplayed cytostatic activity over human pancreatic carcinoma (PaCa-2)cells, as determined through MTS assay. The cytostatic activities recorded foreach of the partitions correlated with their relative uPA inhibitoryactivities. There are no existing reports of uPA inhibitors being present inany of the plants reported in this study.

Inhibitors of urokinase type plasminogen activator and cytostatic activity from crude plants extracts

247th National Meeting (2014)

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