Barac A, et al. – In this present study, the researchers explored the molecular mechanisms of cell death of oral cancer cells caused by treatment with a nonselective Cox–2 inhibitor in combination with a low–dose chemotherapeutic drug. They disclosed that combined treatment of the oral cancer cells with nimesulide and cisplatin increases and induces necrosis and apoptosis through different pathways, compared to the single–drug treatment. They also reported a significant effect of the cytoplasmic increase in histones of cell lines SCC9 and SCC25.

Methods

• Squamous cell carcinoma (SCC) cells SCC9 and SCC25 were subjected to mono– and combination therapy with nimesulide and cisplatin. 
• Fluorescence–activated cell sorting (FACS), immunohistochemistry, high–pressure liquid chromatography (HPLC), microarray gene chips, and isobaric tags for a relative and absolute quantitation (iTRAQ) system were used.

Results

•  After combined exposure, increased numbers of apoptotic and necrotic SCC9/SCC25 cells were detected.
• ATP levels and the energy charge of SCC9 cells were significantly decreased after both individual and combined treatment.
• The researchers detected and quantified a responsible gene, keratin 6a, and 540 relevant proteins.
•  In SCC25 cells, ATP levels significantly decreased only after combination therapy.
• After combined treatment of SCC9 cells, significant upregulation of Histon–H2A/H2B/H4 was found, with a local discovery false rate of 0.003 for Histon–H2A and 0.0027 for Histon–H2B, respectively.