Related Experiment Video

Updated: Jul 5, 2026

Characterization of MLKL-mediated Plasma Membrane Rupture in Necroptosis
08:55

Characterization of MLKL-mediated Plasma Membrane Rupture in Necroptosis

Published on: August 7, 2018

Disruption of MCL1/BOK transmembrane interaction as a novel strategy to induce cell death in tumours

M Buffa1,2, D Leiva1, A Garcia-Jareño1

  • 1Centro de Investigación Príncipe Felipe, Targeted Therapies on Cancer and Inflammation Laboratory, Valencia, Spain.

Cell Death & Disease
|July 3, 2026
PubMed

Insights

Researchers found a way to disrupt the MCL1/BOK transmembrane interaction, selectively killing tumor cells. This approach avoids cardiotoxicity, offering a safer strategy for cancer therapy by targeting transmembrane interactions.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Biochemistry

Background:

  • MCL1, an anti-apoptotic protein, is overexpressed in many cancers, correlating with poor prognosis.
  • Targeting MCL1's cytosolic domain has shown cardiotoxicity in clinical trials.
  • The transmembrane interaction between MCL1 and BOK presents an alternative therapeutic target.

Purpose of the Study:

  • To investigate the disruption of the MCL1/BOK transmembrane interaction for cancer therapy.
  • To evaluate the efficacy and safety of targeting this interaction.
  • To explore the role of BOK in cancer cell death.

Main Methods:

  • Molecular dynamics simulations and LUV-based assays to study the MCL1/BOK interaction.
  • Chemical disruption of the MCL1/BOK transmembrane interaction using MBoIN179.
  • 2D and 3D cell culture models of breast cancer.
  • In vivo studies of tumor growth and metastasis.
  • Analysis of patient tumor microarrays.

Main Results:

  • MBoIN179 disrupted MCL1/BOK transmembrane dimerization, restoring BOK pore formation.
  • Interference with MCL1/BOK interaction promoted BOK relocalization to mitochondria, inducing cancer cell death.
  • Tumor growth and metastasis were reduced in vivo.
  • No observed toxicity in 3D cardiomyocyte cultures.
  • BOK overexpression in aggressive breast cancer subtypes correlates with poor prognosis.

Conclusions:

  • The MCL1/BOK transmembrane interaction is a tumor-selective vulnerability.
  • Targeting this interaction offers a potential therapeutic strategy with cardiac safety.
  • Transmembrane interactions represent viable molecular targets for cancer treatment.

More Related Videos

Cell Death Associated with Abnormal Mitosis Observed by Confocal Imaging in Live Cancer Cells15:53

Cell Death Associated with Abnormal Mitosis Observed by Confocal Imaging in Live Cancer Cells

Published on: August 21, 2013

Detection of Mitochondria Membrane Potential to Study CLIC4 Knockdown-induced HN4 Cell Apoptosis In Vitro13:20

Detection of Mitochondria Membrane Potential to Study CLIC4 Knockdown-induced HN4 Cell Apoptosis In Vitro

Published on: July 17, 2018

Related Concept Videos

Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Drugs that Destabilize Microtubules01:10

Drugs that Destabilize Microtubules

Microtubules are dynamic structures and can be regulated by microtubule targeting agents (MTAs). Microtubule destabilizing drugs are a class of MTAs that destabilize and prevent microtubules' polymerization. Both natural and synthetic chemicals can be found under this class of drugs. Vincristine and vinblastine, two vinca alkaloids, and colchicine were among the first to be discovered. These drugs can affect cells in various ways, either by inducing a change in cell morphology, preventing...
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...