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CYTOTOXIC EFFECT OF IMIDAZOLIUM OXIMES ON PROSTATE CANCER CELLS (PC-3)

Prostate cancer is one of the most common types of cancer and is still difficult to cure with currently available antitumor agents. New compounds showing more efficient antitumor properties are being intensively developed. One of these compounds are imidazolium oximes, since these heterocyclic aromatic structures have numerous pharmacological properties, achieved through various modes of action and interactions with many cellular targets. In view of the therapeutic importance of oximes in suppressing tumor growth, the present study focused on newly synthesized imidazolium oximes ; hydroxyimino-methyl imidazolium bromides (compounds IV, VI, VII and X) in PC-3 prostate cancer cells. Cells were exposed to oximes in a concentration range of 6.25–800 μM for 1 h, 4 h, and 24 h. The effect on cell viability was investigated by monitoring mitochondrial succinate dehydrogenase activity in metabolically active cells by MTS assay. It was then examined whether the tested oximes impaired cell membrane integrity by measuring the activity of the enzyme lactate dehydrogenase (LDH). Finally, flow cytometry was used to elucidate if the tested oximes could induce programmed cell death, apoptosis. The results indicate that tested hydroxyimino-methyl imidazolium bromides caused a significant cytotoxic effect on PC-3 cells, in a time- and dose-dependent manner. Compounds VII and X, having in their structure aromatic side branch, exhibited the highest inhibitory effect on cell viability and induced a significant release of LDH into the medium, which points to the induction of necrosis. Conversely, none of the compounds induced apoptosis, which implies the need for further modification of these oximes in order for them to be suitable in future studies as potential antitumor drugs.

antitumor drugs, cytotoxicity, MTS, LDH, flow cytometry

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