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Discovering and characterizing NQO1 transcript variants in FaDu cancer cells exposed to stress

The stress-related effects of three compounds, cisplatin, curcumin and Tazemetostat, was explored in FaDu cancer cells. These cells originate from hypopharingeal human cancer. In cytotoxic assay, these cells showed the highest sensitivty to curcumin and cisplatin treatment. However, these two compounds had different effects on ROS generation, which was almost eliminated by curcumin, in a dose-dependent manner. With respect to NQO1 which is the stress- related taget of the NRF2 transcription factor, we discovered that some treatments increase the level of NQO1 protein in both, cytoplasmic and nuclar protein fractions. The strongest increase of NQO1 in cytoplasmic fraction was induced by cisplatin and curcumin, while DMSO induced its strongest increase in the nucleus. The size of the detected protein was always app. 30 kDa, regardless of the treatment and/or NQO1 subcellular localisation. However, we were able to detect three transcription variants of NQO1, which were characterized by DNA sequencing. Although these sequences are deposited in the Gene Bank as transcript variants 1, 3, and 4, their simultanous presence in a cell has never been described. While only a transcript variant 1 seems to be translated into the mature protein, still to be discovered is the potential importance of the transcripts corresponding to transcript variants 3 and 4, which do not seem to be translated.

NQO1, stress, splice variants, protein isoforms

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