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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

Induction of apoptosis by quercetin is mediated through AMPKalpha1/ASK1/p38 pathway

Yun-Kyoung Lee1, Jin-Taek Hwang, Dae Young Kwon

  • 1Department of Food and Nutrition, Hannam University Daedeok Valley Campus, 461-6 Jeonmin-dong, Yuseong-gu, Daejeon 305-811, Republic of Korea.

Cancer Letters
|January 20, 2010
PubMed

Insights

Quercetin induces cancer cell death via the ROS/AMPKalpha1/ASK1/p38 pathway. AMP-activated protein kinase alpha 1 (AMPKalpha1) is essential for this quercetin-driven apoptosis signaling cascade.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Pharmacology

Background:

  • Understanding apoptotic pathways is crucial for developing effective cancer prevention and treatment strategies.
  • Quercetin, a flavonoid, has demonstrated potential anti-cancer properties, but its precise molecular mechanisms require further elucidation.

Purpose of the Study:

  • To investigate the regulatory mechanism of quercetin-induced apoptosis.
  • To elucidate the roles of apoptosis signal-regulating kinase (ASK1) and mitogen-activated protein kinase (MAPK) pathways in quercetin's action.
  • To identify key molecular players controlling quercetin-mediated apoptosis.

Main Methods:

  • Assessing quercetin's effect on apoptotic cell death and reactive oxygen species (ROS) generation.
  • Evaluating the activation status of ASK1 and p38.
  • Investigating the role of AMP-activated protein kinase (AMPK) using chemical inhibitors (Compound C) and small interfering RNA (siRNA) against AMPKalpha1.

Main Results:

  • Quercetin treatment led to increased apoptotic cell death, mediated by ROS generation and subsequent ASK1 activation.
  • ASK1 activation was found to be correlated with p38 activation.
  • AMPKalpha1 was identified as a critical regulator, as its inhibition blocked quercetin-induced ASK1/p38 activation.

Conclusions:

  • Quercetin-induced apoptosis involves a signaling pathway comprising ROS, AMPKalpha1, ASK1, and p38.
  • AMPKalpha1 is a necessary component for the apoptotic events triggered by ASK1 activation in response to quercetin.

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