Quercetin nanoparticles display antitumor activity via proliferation inhibition and apoptosis induction in liver cancer cells

Abstract

Quercetin is a potent cancer therapeutic agent and dietary antioxidant present in fruit and vegetables. Quercetin prevents tumor proliferation by inducing cell cycle arrest and is a well known cancer therapeutic agent and autophagy mediator. Recent studies showed that drug delivery by nanoparticles have enhanced efficacy with reduced side effects. In this regard, gold-quercetin into poly(DL-lactide-co-glycolide) nanoparticles was examined. In this study, we explored the role and possible underlying mechanisms of quercetin nanoparticle in regulation of antitumor activity in liver cancer cells. Treatment with quercetin nanoparticle effectively inhibited the liver cancer cell proliferation, cell migration and colony formation, thus suppressing liver cancer progression. Quercetin nanoparticle also upregulated apoptosis markedly. Further study suggested that quercetin nanoparticle accelerated the cleavage of caspase-9, caspase-3, and induced the up-releasing of cytochrome c (Cyto-c), contributing to apoptosis in liver cancer cells. Quercetin nanoparticles also promoted telomerase reverse transcriptase (hTERT) inhibition through reducing AP-2β expression and decreasing its binding to hTERT promoter. In addition, quercetin nanoparticle had an inhibitory role in cyclooxygenase 2 (COX-2) via suppressing the NF-κB nuclear translocation and its binding to COX-2 promoter. Quercetin nanoparticle also inactivated Akt and ERK1/2 signaling pathway. Taken together, our results suggested that quercetin nanoparticle had an antitumor effect by inactivating caspase/Cyto-c pathway, suppressing AP-2β/hTERT, inhibiting NF-κB/COX-2 and impeding Akt/ERK1/2 signaling pathways. Our results provided new mechanistic basis for further investigation of quercetin nanoparticles to find potential therapeutic strategies and possible targets for liver cancer inhibition.

Targeting autophagy using metallic nanoparticles: a promising strategy for cancer treatment

“…Quercetin exhibits beneficial effects on human health and possesses selective antiproliferative and antitumor effects via apoptotic mechanisms on different human cancer cell lines [138]. It has been reported that gold–quercetin nanoparticles, stabilized by PLGA, induce autophagy cell death and apoptosis through dysregulation of signaling pathways in human liver, cervical and neuroglioma cancer cells [139–141]. …”

Antitumor Effects of Quercetin in Hepatocarcinoma In Vitro and In Vivo Models: A Systematic Review

“…Drug delivery systems have emerged as a novel mechanism of targeting cancer progression, enhancing drug efficacy through its encapsulation [42]. In this line, nanomedicine has developed numerous nanoparticles employing either organic-or inorganic-based nanocarriers [40].…”

Floridoside Exhibits Antioxidant Properties by Activating HO-1 Expression via p38/ERK MAPK Pathway

“…In recent years, a great deal of attention has been paid to the application of small-molecule polyhydroxy compounds in liver diseases. Ren et al have reported that quercetin nanoparticles exhibit antitumor activity by inhibiting the proliferation and inducing the apoptosis of liver cancer cells [16]. Hsiang et al have found that silymarin regulates the expressions of genes relevant to apoptosis and oxidative stress in HepG2 cells via the suppression of NF-κB activity [17].…”