Abstract
BackgroundNasopharyngeal carcinoma (NPC) is a unique tumour of epithelial origin with a distinct geographical distribution, genetic predisposition and environmental as well as dietary influence as aetiological factors. Standard NPC treatment regimes, such as radiotherapy and concurrent chemotherapy with cytotoxic drugs, can produce undesirable complications often associated with significant toxicity. Here, we report the effects of a widely distributed flavonoid, quercetin, on cell proliferation, apoptosis and cell cycle arrest. The effects of combining quercetin and cisplatin on human NPC cells were explored.MethodsCell proliferation was monitored by the dynamic, impedance-based cell analyzer (xCELLigence system) and the MTS assay. Ki67 proliferation antigen and fatty acid synthase (FASN) level was examined by Western blotting. Flow cytometry was also carried out to study the effects of quercetin on cell cycle and apoptosis status.ResultsAt 100 μM, quercetin inhibited cell proliferation and decreased expression of FASN and Ki67 antigen. Cell cycle analysis revealed a substantial increase in the proportion of cells in the G2/M phase. We also demonstrated the enhanced cytotoxic effects of quercetin treatment in concomitant with the chemotherapeutic drug, cisplatin, in cultured NPC cells. The combination index (CI) value of quercetin-cisplatin combination was < 1, indicating synergism.ConclusionsOur study showed that quercetin exhibited synergistic effects with cisplatin against NPC cells. Dose-reduction index (DRI) values > 1 implied the possibility of reducing the cisplatin dosage required to treat NPC, with the addition of quercetin. In turn, this could reduce the risk of cisplatin-associated toxicity. The potential of combining quercetin with cisplatin as a chemotherapeutic strategy for treatment of NPC should be explored further.
Highlights
Nasopharyngeal carcinoma (NPC), a disease with distinct ethnic and geographic distribution, is common in Southern China, North Africa and South East Asia including Malaysia [1]
We report the effects of quercetin treatment alone and in combination with cisplatin, in a set of Epstein-Barr virus (EBV)-negative and EBV-positive NPC cell line
Dynamic monitoring of quercetin-treated cells To determine the effect of quercetin on NPC cells, the xCELLigence system, a real-time cell proliferation, viability and cytotoxicity analyzer, was conducted
Summary
Nasopharyngeal carcinoma (NPC), a disease with distinct ethnic and geographic distribution, is common in Southern China, North Africa and South East Asia including Malaysia [1]. Quercetin was reported to inhibit enzymatic activity of fatty acid synthase (FASN) and arrest cell growth [7]. It was shown to effectively inhibit growth in NPC HEN1 cells [8], human head and neck squamous cell carcinoma [9], human leukemic T-cells [10], human gastric cancer HGC-27 cells [11] and modulates Caco-2 human colorectal adenocarcinoma cell proliferation in a biphasic way [12]. We report the effects of quercetin treatment alone and in combination with cisplatin, in a set of EBV-negative and EBV-positive NPC cell line. Standard NPC treatment regimes, such as radiotherapy and concurrent chemotherapy with cytotoxic drugs, can produce undesirable complications often associated with significant toxicity. We report the effects of a widely distributed flavonoid, quercetin, on cell proliferation, apoptosis and cell cycle arrest. The effects of combining quercetin and cisplatin on human NPC cells were explored
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