Combined Treatment of Cancer Cells Using Allyl Palladium Complexes Bearing Purine-Based NHC Ligands and Molecules Targeting MicroRNAs miR-221-3p and miR-222-3p: Synergistic Effects on Apoptosis
Combined treatments employing lower concentrations of different drugs are used and
studied to develop new and more effective anticancer therapeutic approaches. The combination
therapy could be of great interest in the controlling of cancer. Regarding this, our research group
has recently shown that peptide nucleic acids (PNAs) that target miR-221 are very effective and
functional in inducing apoptosis of many tumor cells, including glioblastoma and colon cancer
cells. Moreover, in a recent paper, we described a series of new palladium allyl complexes showing
a strong antiproliferative activity on different tumor cell lines. The present study was aimed to
analyze and validate the biological effects of the most active compounds tested, in combination
with antagomiRNA molecules targeting two miRNAs, miR-221-3p and miR-222-3p. The obtained
results show that a “combination therapy”, produced by combining the antagomiRNAs targeting
miR-221-3p, miR-222-3p and the palladium allyl complex 4d, is very effective in inducing apoptosis,
supporting the concept that the combination treatment of cancer cells with antagomiRNAs targeting
a specific upregulated oncomiRNAs (in this study miR-221-3p and miR-222-3p) and metal-based
compounds represents a promising therapeutic strategy to increase the efficacy of the antitumor
protocol, reducing side effects at the same time