INTRACELLULAR MOLECULAR-INTERACTIONS OF ANTITUMOR DRUG AMSACRINE (M-AMSA) AS REVEALED BY SURFACE-ENHANCED RAMAN-SPECTROSCOPY

Cytotoxicity of several classes of antitumor DNA intercalators is thou ght to result from disturbance of DNA metabolism following trapping of the nuclear enzyme DNA topoisomerase II as a covalent complex on DNA. Here, molecular interactions of the potent antitumor drug amsacrine ( m-AMSA), an inhibitor of topoisomerase II, within living K562 cancer c ells have been studied using surface-enhanced Raman (SER) spectroscopy . The work is based on data of the previously performed model SER expe riments dealing with amsacrine/DNA, drug/topoisomerase II and drug/DNA /topoisomerase II complexes in aqueous buffer solutions. The SER data indicated two kinds of amsacrine interactions in the model complexes w ith topoisomerase II alone or within ternary complex: non-specific (vi a the acridine moiety) and specific to the enzyme conformation (via th e side chain of the drug). These two types of interactions have been b oth revealed by the micro-SER spectra of amsacrine within living K562 cancer cells. Our data suppose the specific interactions of amsacrine with topoisomerase II via the side chain of the drug (particular featu re of the drug/topoisomerase II and ternary complexes) to be crucial f or its inhibitory activity.