Combination of hesperetin and platinum enhances anticancer effect on lung adenocarcinoma

Biomed Pharmacother. 2019 May:113:108779. doi: 10.1016/j.biopha.2019.108779. Epub 2019 Mar 16.

Abstract

Lung cancer remains the leading cause of oncological death. There is an urgent need to discover new molecular targets and to develop new treatments. One of the UDP-glucuronosyltransferases (UGTs) family, UGT1A3, is highly expressed in lung adenocarcinoma (LUAD), and is associated with poor prognosis. Its inhibitor, hesperetin, may play an important role in anticancer therapy. The purpose of this study was to investigate the role of UGT1A3 in the progression of lung adenocarcinoma and to explore the value of its inhibitor hesperetin in the treatment of LUAD. Hesperetin suppressed lung adenocarcinoma cell proliferation and migration. The combination treatment of hesperetin with platinum suppressed tumor progression more significantly, especially compared with single drug treatment. UGT1A3 is an important prognostic factor for LUAD, and hesperetin can synergize platinum drugs by inhibiting UGT1A3 and increasing levels of reactive oxygen species (ROS).

Keywords: Hesperetin; Lung cancer; UDP-glucuronosyltransferases.

Publication types

  • Comparative Study

MeSH terms

  • A549 Cells
  • Adenocarcinoma of Lung / drug therapy*
  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Cell Proliferation / drug effects
  • Disease Progression
  • Glucuronosyltransferase / antagonists & inhibitors*
  • Glucuronosyltransferase / metabolism
  • Hesperidin / administration & dosage
  • Humans
  • Lung Neoplasms / drug therapy*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Platinum Compounds / administration & dosage
  • Reactive Oxygen Species / metabolism
  • Xenograft Model Antitumor Assays

Substances

  • Platinum Compounds
  • Reactive Oxygen Species
  • Hesperidin
  • UDP-glucuronosyltransferase, UGT1A3
  • Glucuronosyltransferase
  • hesperetin