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The dietary compound luteolin inhibits pancreatic cancer growth by targeting BCL-2

Zhimei Li1, Yiyuan Zhang, Lixia Chen

  • 1Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. li_hua@hust.edu.cn.

Food & Function
|May 18, 2018
PubMed

Insights

Luteolin, a natural compound, directly targets and inhibits the BCL-2 protein in pancreatic cancer cells. This inhibition triggers apoptosis and reduces tumor growth, suggesting potential as a novel cancer therapy.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Research

Background:

  • Overexpression of the BCL-2 protein promotes cancer cell survival and treatment resistance.
  • BCL-2 is amplified in SW1990 pancreatic cancer cells, correlating with poor patient outcomes.
  • Targeting BCL-2 with natural antagonists offers potential therapeutic benefits.

Purpose of the Study:

  • To identify natural small-molecule inhibitors of BCL-2.
  • To investigate the therapeutic potential of luteolin in pancreatic cancer.
  • To elucidate the mechanism by which luteolin induces cancer cell death.

Main Methods:

  • Structure-based virtual ligand screening identified luteolin as a BCL-2 inhibitor.
  • Cellular thermal shift assay (CETSA) and microscale thermophoresis (MST) confirmed direct binding of luteolin to BCL-2.
  • In vitro proapoptotic assays and in vivo xenograft models assessed luteolin's efficacy.

Main Results:

  • Luteolin demonstrated dose-dependent, BCL-2-mediated proapoptotic activity in SW1990 cells.
  • Luteolin directly binds to BCL-2, displacing BAX and inducing mitochondrial permeabilization.
  • Luteolin significantly inhibited tumor growth in a SW1990 xenograft mouse model.

Conclusions:

  • Luteolin effectively triggers apoptosis in SW1990 pancreatic cancer cells by targeting BCL-2.
  • Luteolin's mechanism involves direct binding to BCL-2, leading to BAX displacement and cell death.
  • Luteolin shows promise as a potential therapeutic agent for pancreatic cancer.

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