STABILITY OF ARTEMISININ IN AQUEOUS ENVIRONMENTS - IMPACT ON ITS CYTOTOXIC ACTION TO EHRLICH ASCITES TUMOR-CELLS

We have recently shown artemisinin to be cytotoxic against Ehrlich asc ites tumour cells. The aim of this study was to investigate the stabil ity of this compound in the aqueous environment of the in-vitro Ehrlic h ascites tumour cell system (RPMI 1640 cell culture medium supplement ed with 10% foetal bovine serum (RPMI/FBS) with reference to its cytot oxic action. Literature data show that artemisinin can react with Fe2 yielding reactive intermediates leaving artemisinin G as a major end- product. The current study showed that only excess addition of Fe2+ to artemisinin in distilled water, phosphate-buffered saline (PBS) and R PMI/FBS and incubation for 24 h led to degradation of artemisinin and yielded artemisinin G. If Fe was not added results from HPLC analysis were indicative of complete recovery of artemisinin from distilled wat er and RPMI/FBS, with or without cells, at 37 degrees C for at least 2 4 h. In addition, incubation of artemisinin in RPMI/FBS with or withou t cells at 37 degrees C for 24 h before cytotoxicity assay did not cha nge its cytotoxic action. On the basis of these results, we suggest th at cytotoxicity to tumour cells was caused by unchanged artemisinin. T his is not so for the antimalarial activity of artemisinin and derivat ives, for which the presence of a pool of (haem) Fe2+ is a prerequisit e resulting in free radicals or electrophilic intermediates or both.