Quercetin induces apoptosis and enhances 5-FU therapeutic efficacy in hepatocellular carcinoma

Tumour Biol. 2016 May;37(5):6307-13. doi: 10.1007/s13277-015-4501-0. Epub 2015 Dec 1.

Abstract

Quercetin (Q), a flavonoid compound, which is obtained in variety of fruits, seeds, and vegetables, has been reported to possess many pharmacological properties including cancer-preventive and anticancer effects. However, studies on the anticancer effects and underlying mechanisms of Q in human hepatocellular carcinoma (HCC) are still limited. The present study is conducted to investigate the anticancer efficacy and adjuvant chemotherapy action of Q in HCC. HCC cell lines HepG2 and SMCC-7721 were treated with different concentrations of Q. The antiproliferative effects of Q were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), and the apoptosis and cell cycle dynamics were assessed by flow cytometry; the expression of apoptosis-associated proteins were evaluated by Western blot and immunohistochemistry staining; the tumor growth in vivo was evaluated in a xenograft mouse model. Our results showed that Q effectively inhibited human HCC cell proliferation and induced apoptosis by upregulating the expression of Bad and Bax and downregulating the expression of Bcl-2 and Survivin in vitro. Furthermore, Q obviously inhibited the tumor growth and enhanced the 5-fluorouracil (5-FU) therapeutic efficacy in vitro and in vivo. Taken together, our findings highlight that Q effectively inhibited the growth of tumor and enhanced the sensitivity to thermotherapy, indicating Q is a potential treatment option for HCC.

Keywords: Apoptosis; Cell proliferation; Hepatocellular carcinoma; Quercetin.

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols
  • Apoptosis / drug effects
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / pathology
  • Cell Proliferation / drug effects
  • Fluorouracil / administration & dosage*
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / pathology
  • Mice
  • Quercetin / administration & dosage*
  • Xenograft Model Antitumor Assays

Substances

  • Quercetin
  • Fluorouracil