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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

MDR1 up-regulated by apoptotic stimuli suppresses apoptotic signaling

Toshiyuki Sakaeda1, Tsutomu Nakamura, Midori Hirai

  • 1Department of Hospital Pharmacy, School of Medicine, Kobe University, Japan. sakaedat@med.kobe-u.ac.jp

Pharmaceutical Research
|October 31, 2002
PubMed
Abstract

Insights

Multidrug resistance protein 1 (MDR1) is upregulated by apoptosis-inducing stimuli. MDR1 overexpression suppresses apoptotic signaling, particularly through the mitochondrial pathway, in cancer cells.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • The multidrug resistance 1 (MDR1) P-glycoprotein and related transporters are implicated in apoptosis regulation.
  • Limited information exists regarding the specific role of MDR1 in apoptosis.

Purpose of the Study:

  • To investigate the effect of apoptotic stimuli on MDR1 mRNA expression.
  • To examine the impact of MDR1 on apoptotic signaling pathways in MDR1-overexpressing cells.

Main Methods:

  • Real-time quantitative PCR was used to measure mRNA levels of MDR1, MRP1, MRP2, p53, p21, Bax, and Bcl-2.
  • HeLa cells and MDR1-overexpressing sublines were treated with cisplatin (CDDP) to induce apoptosis.
  • Caspase 3, 8, and 9 activities were assessed following CDDP treatment.

Main Results:

  • MDR1 mRNA expression was rapidly upregulated upon exposure to CDDP.
  • The increase in the Bax/Bcl-2 mRNA ratio induced by CDDP was attenuated in MDR1-overexpressing cells.
  • CDDP-induced increases in caspase 3 and 9 activities were suppressed in MDR1-overexpressing cells.

Conclusions:

  • MDR1 is upregulated by apoptotic stimuli.
  • MDR1 overexpression suppresses apoptotic signaling, likely through the mitochondrial pathway.

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