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Updated: Jan 22, 2026

High-resolution Respirometry to Assess Mitochondrial Function in Permeabilized and Intact Cells
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High-resolution Respirometry to Assess Mitochondrial Function in Permeabilized and Intact Cells

Published on: February 8, 2017

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Raptinal bypasses BAX, BAK, and BOK for mitochondrial outer membrane permeabilization and intrinsic apoptosis

Sina Heimer1, Gertrud Knoll2, Klaus Schulze-Osthoff3,4

  • 1Department of Oral and Maxillofacial Surgery, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, 93053, Regensburg, Germany.

Cell Death & Disease
|July 21, 2019
PubMed

Insights

A novel small molecule, Raptinal, effectively eliminates cancer cells by triggering apoptosis independently of BAX, BAK, and BOK. This compound offers a promising new therapeutic strategy for cancers with defects in the intrinsic apoptosis pathway.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Most cancer chemotherapies induce apoptosis via the intrinsic mitochondrial pathway, relying on BAX, BAK, and BOK proteins.
  • The activation threshold of BAX and BAK influences cancer cell apoptosis sensitivity, posing challenges for targeted therapies.
  • Loss of BAX/BAK function can lead to therapeutic resistance in cancer treatment.

Purpose of the Study:

  • To identify a novel therapeutic agent that can overcome BAX/BAK-dependent apoptosis resistance in cancer cells.
  • To investigate the mechanism of action of Raptinal in inducing cancer cell death.
  • To evaluate the efficacy of Raptinal as a potential anti-cancer drug.

Main Methods:

  • Utilized a small molecule, Raptinal, to investigate its effect on cancer cell apoptosis.
  • Assessed cytochrome c release and mitochondrial function following Raptinal treatment.
  • Evaluated Raptinal's efficacy in vitro and in vivo cancer models.

Main Results:

  • Raptinal triggers cytochrome c release and apoptosis independently of BAX, BAK, and BOK.
  • Raptinal exhibits a dual cytotoxic effect by activating intrinsic apoptosis and shutting down mitochondrial function.
  • Raptinal demonstrated efficacy in eliminating cancer cells in vivo, including in models with apoptosis pathway defects.

Conclusions:

  • Raptinal represents a novel therapeutic strategy for cancer, bypassing BAX/BAK/BOK dependency.
  • The dual mechanism of Raptinal offers a potent anti-cancer effect, even in resistant cancer types.
  • Raptinal shows potential for treating difficult-to-treat cancers with intrinsic apoptosis pathway defects.

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