Chlorogenic Acid Interaction with Cisplatin and Oxaliplatin: Studies in Cervical Carcinoma Cells

摘要

The antiproliferative effect of the naturally occurring polyphenol chlorogenic acid (CGA) was evaluated in combination with either cisplatin or oxaliplatin in human cervical carcinoma cell lines that were either sensitive (A431) or resistant to cisplatin (A431Pt), in order to provide evidence to overcome drug resistance. Cytotoxicity of platinating drugs (IC50 similar to 10(-6) - 10(-5) M) was enhanced by 1-2 orders of magnitude by increasing incubation times (1, 4, and 24 hours) in the two cell lines. CGA treatment presented low cytotoxicity per se (IC50 similar to 10(-4) M at 24 h) if compared with platinum drugs and its activity was similar in A431Pt cells and in their sensitive A431 counterpart. The combination of the platinating drugs with CGA (10(-6) - 10(-4) M) indicated variable effects on cytotoxicity, ranging from potentiation to various degrees of antagonism (in A431 cells) and no effect (in A431Pt cells). In order to explain the different cytotoxic activity elicited by oxaliplatin and cisplatin in association with CGA, the possible presence of chemical interactions was investigated by HPLC analysis. The drug association with CGA caused evident changes in their chromatographic profile, suggesting occurrence of in vitro chemical interactions.