Oral cancer is a cause of
cancer-associated mortality worldwide and the treatment of
oral cancer includes radiation, surgery and
chemotherapy.
Quercetin is a component from natural plant products and it has been demonstrated that
quercetin is able to induce cytotoxic effects through induction of cell apoptosis in a number of human
cancer cell lines. However, there is no available information to demonstrate that
quercetin is able to induce apoptosis in human
oral cancer cells. In the present study, the effect of
quercetin on the cell death via the induction of apoptosis in human
oral cancer SAS cells was investigated using flow cytometry,
Annexin V/
propidium iodide (PI) double staining, western blotting and confocal
laser microscopy examination, to test for cytotoxic effects at 6-48 h
after treatment with
quercetin. The rate of cell death increased with the duration of
quercetin treatment based on the results of a cell viability assay, increased
Annexin V/PI staining, increased
reactive oxygen species and Ca2+ production, decreased the levels of mitochondrial membrane potential (ΔΨm), increased proportion of apoptotic cells and altered levels of apoptosis-associated
protein expression in SAS cells. The results from western blotting revealed that
quercetin increased Fas,
Fas-Ligand, fas-associated
protein with death domain and
caspase-8, all of which associated with cell surface
death receptor. Furthermore,
quercetin increased the levels of activating
transcription factor (ATF)-6α, ATF-6β and
gastrin-releasing peptide-78 which indicated an increase in endoplasm reticulum stress, increased levels of the
pro-apoptotic protein BH3 interacting-domain death antagonist, and decreased levels of
anti-apoptotic proteins B-cell lymphoma (Bcl) 2 and Bcl-extra large which may have led to the decreases of ΔΨm. Additionally, confocal microscopy suggested that
quercetin was able to increase the expression levels of
cytochrome c,
apoptosis-inducing factor and
endonuclease G, which are associated with apoptotic pathways. Therefore, it is hypothesized that
quercetin may potentially be used as a novel anti-
cancer agent for the treatment of
oral cancer in future.