From a Cochineal Dye to the Possibility of an Anticancer Agent: Free Radical-Mediated Activity of Carminic Acid and Its CoII Complex on Nucleobases, DNA, and PC3 Prostate Carcinoma Cells.

Anthracycline-based anticancer agents perform through different modes; the free radical pathway is just one of them. Although they are effective anticancer agents, for different reasons, there is a lookout for simpler analogs that mimic their actions. Carminic acid, having a close resemblance to anthracyclines, and its CoII-complex were investigated for activity related to the generation of semiquinone. The compounds were reduced at their respective reduction potentials, which were previously identified using cyclic voltammetry. Interactions between reduced species of the compounds and biological targets (nucleobases or DNA) maintained in the immediate vicinity of the generation of reduced species were monitored, enabling a realization of what might happen when anthracyclines are reduced within cells. Changes caused to nucleobases were realized using HPLC, while those in DNA were followed by monitoring the decrease in fluorescence when the target DNA was subsequently treated with ethidium bromide. Results indicate that, in the presence of the CoII-complex, the damage observed in uracil was approximately double, and that in cytosine and guanine was one and a half times greater than that observed when carminic acid was used as the sensitizer. For thymine and adenine, there was no significant difference in the results whether performed in the presence of carminic acid or its CoII-complex. Studies on calf thymus DNA indicate modification caused in presence of the complex was one and a half times more than when carminic acid was used. Results indicate that the reduced species formed on the complex were more inclined to interact with cytosine and guanine than with thymine and adenine. Studies on PC3 (carcinoma) and WI-38 (normal) cells reveal that the complex was more effective on carcinoma cells. On WI-38, both compounds show relatively high IC50 values, suggesting they weren't much affected. Since DCFDA assay helps in realizing aspects related to ROS generation, increased ROS production provides an explanation for the reactivity of compounds on nucleobases, DNA, and cells. Hence, it may be said there is a strong possibility simpler anthracycline analogs like carminic acid and its CoII complex could be effective as anticancer agents like the anthracyclines.