Quercetin induced apoptosis of human oral cancer SAS cells through mitochondria and endoplasmic reticulum mediated signaling pathways

Abstract

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.

Antioxidant, Antiproliferative and Apoptosis-Inducing Efficacy of Fractions from Cassia fistula L. Leaves

“…Gao et al [54] reported that kaempferol induced extrinsic apoptosis through the death receptors/FADD/Caspase-8 pathway in human ovarian cancer A2780/CP70 cells. Quercetin treatment induced apoptosis in human oral cancer SAS cells by increasing the expression of Fas, Fas-Ligand, and caspase-8 [55]. Epiafzelechin was shown to downregulate anti-apoptotic protein Bcl-xl, of the Bcl-2 family as detected by western blot analysis (Figure 16).…”

Wine Consumption and Oral Cavity Cancer: Friend or Foe, Two Faces of Janus

“…MMPs inhibition occurs via the down-regulation of protein kinase C and the blocking of mitogen activated protein kinases (MAPK) and phosphatidylinositide-3 kinases (PI3K) signaling pathways and both cyclo-oxygenase-2 (COX-2) and NF-κB [93]. Moreover, quercetin affects the ratio of anti-/pro-apoptotic proteins in SAS cell lines, which may lead to the dysfunction of mitochondria followed by the release of cytochrome c (cyto c), apoptosis-inducing factors and endonuclease G from mitochondria, inducing cell-destruction by triggering apoptosis [94].…”

Quercetin Inhibits Cell Survival and Metastatic Ability via the EMT-Mediated Pathway in Oral Squamous Cell Carcinoma

“…The 10-40 µM quercetin concentration used in this study is commonly used for cancer cells under 24-h treatment conditions. Quercetin, a flavonoid found in many fruits, vegetables, and grains, has been shown to have an antitumor effect on OSCC cells via the induction of cell cycle arrest [29,40]. Quercetin treatment suppressed cell growth by inducing G2/M arrest and apoptosis in EGFR-overexpressing HSC-3 and TW206 oral cancer cells [30].…”

“…Previous studies have reported the antibacterial effects of quercetin against Actinobacillus actinomycetemcomitans (Aa) and Porphyromonas gingivalis (Pg), which are the major pathogens in PD [27,28]. Moreover, recently, studies have reported that quercetin inhibits the cell viability, migration, and invasion of OSCC cells [29][30][31][32]. However, its potential actions in OSCCs have been poorly explored.…”