334
Views
48
CrossRef citations to date
0
Altmetric
Original Articles

New Approach for Treatment of Primary Liver Tumors: The Role of Quercetin

, , , , , , , , & show all
Pages 250-266 | Received 13 Apr 2015, Accepted 08 Nov 2015, Published online: 04 Mar 2016
 

abstract

Hepatocellular carcinoma (HCC) is the most common primary liver tumor (PLT), with cholangiocarcinoma (CC) being the second most frequent. Glucose transporter 1 (GLUT-1) expression is increased in PLTs and therefore it is suggested as a therapeutic target. Flavonoids, like quercetin, are GLUT-1 competitive inhibitors and may be considered as potential therapeutic agents for PLTs. The objective of this study was evaluation of quercetin anticancer activity in three human HCC cell lines (HepG2, HuH7, and Hep3B2.1–7) and in a human CC cell line (TFK-1). The possible synergistic effect between quercetin and sorafenib, a nonspecific multikinase inhibitor used in clinical practice in patients with advanced HCC, was also evaluated. It was found that in all the cell lines, quercetin induced inhibition of the metabolic activity and cell death by apoptosis, followed by increase in BAX/BCL-2 ratio. Treatment with quercetin caused DNA damage in HepG2, Hep3B2.1–7, and TFK-1 cell lines. The effect of quercetin appears to be independent of P53. Incubation with quercetin induced an increase in GLUT-1 membrane expression and a consequent reduction in the cytoplasmic fraction, observed as a decrease in 18F-FDG uptake, indicating a GLUT-1 competitive inhibition. The occurrence of synergy when sorafenib and quercetin were added simultaneously to HCC cell lines was noticed. Thus, the use of quercetin seems to be a promising approach for PLTs through GLUT-1 competitive inhibition.

Acknowledgments

The authors thank Bayer Healthcare for the availability of sorafenib.

Ana Filipa Brito would like to thank the Portuguese Foundation for Science and Technology for the award of a PhD scholarship (SFRH/BD/61378/2009).

Ana Catarina Mamede would like to thank the Portuguese Foundation for Science and Technology for the award of a PhD scholarship (SFRH/BD/73649/2010).

Mafalda Laranjo would like to thank the Portuguese Foundation for Science and Technology for the award of a PhD scholarship (SFRH/BD/44957/2008).

The authors thank CIMAGO for financing the project 09/12.

The authors also thank FCT, Portugal (Strategic Project PEst-C/SAU/UI3282/2013 and UID/NEU/04539/2013), COMPETE-FEDER.

Conflict of Interest: None.

Log in via your institution

Log in to Taylor & Francis Online

PDF download + Online access

  • 48 hours access to article PDF & online version
  • Article PDF can be downloaded
  • Article PDF can be printed
USD 53.00 Add to cart

Issue Purchase

  • 30 days online access to complete issue
  • Article PDFs can be downloaded
  • Article PDFs can be printed
USD 633.00 Add to cart

* Local tax will be added as applicable

Related Research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.