The roles of endoplasmic reticulum stress and mitochondrial apoptotic signaling pathway in quercetin‐mediated cell death of human prostate cancer PC‐3 cells

Abstract

Prostate cancer has its highest incidence and is becoming a major concern. Many studies have shown that traditional Chinese medicine exhibited antitumor responses. Quercetin, a natural polyphenolic compound, has been shown to induce apoptosis in many human cancer cell lines. Although numerous evidences show multiple possible signaling pathways of quercetin in apoptosis, there is no report to address the role of endoplasmic reticulum (ER) stress in quercetin-induced apoptosis in PC-3 cells. The purpose of this study was to investigate the effects of quercetin on the induction of the apoptotic pathway in human prostate cancer PC-3 cells. Cells were treated with quercetin for 24 and 48 h and at various doses (50-200 μM), and cell morphology and viability decreased significantly in dose-dependent manners. Flow cytometric assay indicated that quercetin at 150 μM caused G0/G1 phase arrest (31.4-49.7%) and sub-G1 phase cells (19.77%) for 36 h treatment and this effect is a time-dependent manner. Western blotting analysis indicated that quercetin induces the G0/G1 phase arrest via decreasing the levels of CDK2, cyclins E, and D proteins. Quercetin also stimulated the protein expression of ATF, GRP78, and GADD153 which is a hall marker of ER stress. Furthermore, PC-3 cells after incubation with quercetin for 48 h showed an apoptotic cell death and DNA damage which are confirmed by DAPI and Comet assays, leading to decrease the antiapoptotic Bcl-2 protein and level of ΔΨm , and increase the proapoptotic Bax protein and the activations of caspase-3, -8, and -9. Moreover, quercetin promoted the trafficking of AIF protein released from mitochondria to nuclei. These data suggest that quercetin may induce apoptosis by direct activation of caspase cascade through mitochondrial pathway and ER stress in PC-3 cells.

Expression of prostate stem cell antigen is downregulated during flavonoid-induced cytotoxicity in prostate cancer cells

“…Analogous to previous studies in human prostate cancer cells (24,(28)(29)(30), the present study demonstrated that genistein, luteolin and quercetin induced apoptosis in DU145 cells. Thus, genistein, luteolin and quercetin may inhibit the growth of prostate cancer cells through the induction of cell cycle arrest and apoptosis.…”

“…Similarly, previous studies have demonstrated that flavonoids inhibit cell growth by inducing S phase cell cycle arrest in prostate cancer cells (19)(20)(21). Flavonoids have also been documented to arrest cell-cycle progression at G0/G1 and G2/M in prostate cancer cells (22)(23)(24). These results indicate that flavonoids may block cell growth at multiple stages of the cell cycle (25).…”

Enhancing Antioxidant Cellular Defense by Using Quercetin Loaded TiO2 Nanoparticles in Swiss 3T3 Albino Mouse Fibroblast Cells

“…Two major phenomena concerning apoptosis occured that are related to, cleavage of cas 3 and parp proteins, determined in the Q-Cntrl groups at 6 and 12 h ( Figure 3C and 3D). Cas 3 is the most common executioner caspase [31] and extinguishes cell by cleaving parp [32]. Our results clearly demonstrated that quercetin caused cell death at high concentration through cas 3 dependent apoptotic pathway ( Figure 3C).…”

Fisetin Induces Apoptosis of HSC3 Human Oral Cancer Cells Through Endoplasmic Reticulum Stress and Dysfunction of Mitochondria-mediated Signaling Pathways

“…For ΔΨ m measurement, cells were isolated and re-suspended with 500 μl of 3,3'-dihexyloxacarbocyanine iodide (DiOC 6 ) (Sigma Chemical Co.) (4 μmol/l) and maintained in the dark for 30 minutes. After incubation, all samples were analyzed by flow cytometry as described previously (33)(34)(35). in vivo 31: 1103-1114 (2017) Measurements of caspase activities.…”