Quercetin induces cell death in cervical cancer by reducing O-GlcNAcylation of adenosine monophosphate-activated protein kinase

Abstract

Hyper-O-GlcNAcylation is a general feature of cancer which contributes to various cancer phenotypes, including cell proliferation and cell growth. Quercetin, a naturally occurring dietary flavonoid, has been reported to reduce the proliferation and growth of cancer. Several reports of the anticancer effect of quercetin have been published, but there is no study regarding its effect on O-GlcNAcylation. The aim of this study was to investigate the anticancer effect of quercetin on HeLa cells and compare this with its effect on HaCaT cells. Cell viability and cell death were determined by MTT and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelling assays. O-GlcNAcylation of AMP-activated protein kinase (AMPK) was examined by succinylated wheat germ agglutinin pulldown and immunoprecipitation. Immunofluorescence staining was used to detect the immunoreactivitiy of O-linked N-acetylglucosamine transferase (OGT) and sterol regulatory element binding protein 1 (SREBP-1). Quercetin decreased cell proliferation and induced cell death, but its effect on HaCaT cells was lower than that on HeLa cells. O-GlcNAcylation level was higher in HeLa cells than in HaCaT cells. Quercetin decreased the expression of global O-GlcNAcylation and increased AMPK activation by reducing the O-GlcNAcylation of AMPK. AMPK activation due to reduced O-GlcNAcylation of AMPK was confirmed by treatment with 6-diazo-5-oxo-L-norleucine. Our results also demonstrated that quercetin regulated SREBP-1 and its transcriptional targets. Furthermore, immunofluorescence staining showed that quercetin treatment decreased the immunoreactivities of OGT and SREBP-1 in HeLa cells. Our findings demonstrate that quercetin exhibited its anticancer effect by decreasing the O-GlcNAcylation of AMPK. Further studies are needed to explore how quercetin regulates O-GlcNAcylation in cancer.

Systems Pharmacology Study of the Anticervical Cancer Mechanisms of FDY003

“…[153][154][155][156][157][158][159][160][161] Quercetin exerts anticancer effects in cervical cancer cells by regulating their dysregulated behaviors in proliferation, cell cycle progression, survival, apoptosis, migration, and invasion. 135,[161][162][163][164][165][166][167][168][169][170][171][172][173][174] Isorhamnetin suppresses the proliferation of cervical cancer cells by inducing cell cycle arrest in the G2/M phase. 175 Cordycepin stimulates apoptotic cell death and interferes with the cell cycle through the generation of reactive oxygen species and the repression of cell cycle regulators in cervical cancer cells, 176,177 and sensitizes cervical cancer cells to radiotherapy.…”

Cytotoxicity Potential of Nelsonia canescens (Lam.) Spreng Extracts against Cervical Cancer Cell Lines

“…According to numerous studies, Luteolin is known for it potent prevention and inhibition against cervical cancer [26]. Quercetin decreased cervical cancer cell proliferation and induced cell death [27]. It is showed that caffeic acid isolated from several kinds of vegetables and herbals had anti-proliferative effects on cervical cancer cell lines, this compound can significantly reduce the proliferation of HeLa cells in a time-dependent manner [28].…”

Cyclosporin A aggravates hydrogen peroxide-induced cell death in kidney proximal tubule epithelial cells

“…A yellow water soluble tetrazolium dye thiazolyl blue tetrazolium bromide (MTT; Biosesang, Seongnam, Korea) was used to measure cell viability as described previously [2728]. After removing the culture medium, cells were incubated at 37℃ with 5 mg/ml MTT in PBS for 30 minutes.…”