Quercetin Induces Apoptosis in Human Salivary Adenoid Cystic Carcinoma Cells

Objectives: Adenoid cystic carcinoma (ACC) is a highly malignant tumor that is generally unresponsive or only weakly responsive to the currently available antineoplastic agents. Thus novel therapeutic strategies and agents are urgently needed to treat this incurable cancer. Quercetin, the most common flavonoid in nature, has been reported to possess significant anti-tumor activity both in vitro and in vivo. The present study was to investigate the anti-growth effect of quercetin on human salivary adenoid cystic carcinoma (ACC) cells.

Methods: ACC-2 (low metastasis) and ACC-M (high metastasis) cell lines were set up to evaluate the effect of quercetin on cell proliferation and apoptosis, as well as the possible underlying mechanisms.

Results: The MTT assay showed that quercetin concentration- and time-dependently decreased the cell viability in both ACC-2 (low metastasis) and ACC-M (high metastasis) cells. Moreover, by employing Hoechst 33258 staining, Cell Death Detection ELISA^PLUS assay, cell cycle analysis, and Annexin V-FITC/propidium iodide double-labeling, it was established that treatment with quercetin resulted in significant apoptosis of ACC cells. Most importantly, the data also revealed that the apoptosis induced by quercetin was through a mitochondria-dependent pathway evidenced by attenuated mitochondrial membrane potential, released cytochrome c, activated caspase-3, cleaved PARP, as well as increased Bax/Bcl-2 ratio, showing close correlation with the suppression of nuclear factor-kB (NF-kB) activity and down-regulation of vascular endothelial growth factor (VEGF) production.

Conclusions: Our results implicated that further clinical investigation should be warranted to apply quercetin as a novel treatment or prevention regimen for ACC due to its suppression of NF-kB activity and VEGF production leading to significant mitochondrial-dependent apoptosis.