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Combination of hesperetin and platinum enhances anticancer effect on lung adenocarcinoma

Yadong Wang1, Shaorui Liu1, Wei Dong2

  • 1Institute of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, 324 Jingwu Road, Jinan, 250021, PR China.

Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie
|March 20, 2019
PubMed

Insights

Hesperetin inhibits UDP-glucuronosyltransferases (UGTs) like UGT1A3, suppressing lung adenocarcinoma progression. It synergizes with platinum drugs, offering a new therapeutic strategy for lung cancer.

Area of Science:

  • Oncology
  • Biochemistry

Background:

  • Lung cancer is a leading cause of cancer death, necessitating novel therapeutic targets.
  • UDP-glucuronosyltransferases (UGTs), specifically UGT1A3, are upregulated in lung adenocarcinoma (LUAD) and linked to poor patient outcomes.

Purpose of the Study:

  • To elucidate the role of UGT1A3 in LUAD progression.
  • To evaluate the therapeutic potential of hesperetin, a UGT1A3 inhibitor, in LUAD treatment.

Main Methods:

  • Investigated the effect of hesperetin on LUAD cell proliferation and migration.
  • Assessed the combined efficacy of hesperetin and platinum-based chemotherapy in preclinical models.
  • Analyzed the mechanism involving UGT1A3 inhibition and reactive oxygen species (ROS) generation.

Main Results:

  • Hesperetin demonstrated significant suppression of LUAD cell proliferation and migration.
  • Combination therapy with hesperetin and platinum agents markedly enhanced tumor suppression compared to monotherapy.
  • UGT1A3 was confirmed as a critical prognostic factor in LUAD.

Conclusions:

  • Hesperetin exhibits anticancer activity in LUAD by inhibiting UGT1A3.
  • Hesperetin enhances the efficacy of platinum drugs through UGT1A3 inhibition and increased ROS levels.
  • Targeting UGT1A3 with hesperetin represents a promising strategy for LUAD treatment, particularly in combination with platinum chemotherapy.
Keywords:
HesperetinLung cancerUDP-glucuronosyltransferases

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