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Ramucirumab induces apoptosis in Caco-2 cells via mitochondrial impairment and caspase activation

Amal M Al-Dogmi1, Khalid Mashay Al-Anazi1, Wajhul Qamar2

  • 1Department of Zoology, College of Science, King Saud University, P.O. Box 2455, 11451, Riyadh, Saudi Arabia.

Saudi Pharmaceutical Journal : SPJ : the Official Publication of the Saudi Pharmaceutical Society
|June 18, 2026
PubMed

Insights

Ramucirumab induces colorectal cancer cell death by triggering apoptosis through mitochondrial dysfunction and caspase activation, revealing anti-cancer effects beyond angiogenesis inhibition.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Ramucirumab, a VEGFR-2 inhibitor, is known for anti-angiogenesis effects in various cancers.
  • Direct cytotoxic mechanisms of ramucirumab in colorectal cancer, particularly involving mitochondrial dysfunction and ROS-mediated apoptosis, require further elucidation.

Purpose of the Study:

  • To investigate the role of mitochondrial dysfunction, oxidative stress, and caspase activation in ramucirumab-induced cytotoxicity in Caco-2 colorectal cancer cells.

Main Methods:

  • Cell viability (MTT) and cytotoxicity (LDH) assays were performed.
  • Flow cytometry analyzed apoptosis and cell cycle distribution.
  • Staining assessed nuclear condensation, mitochondrial membrane potential (ΔΨm), and intracellular reactive oxygen species (ROS).
  • Expression of caspase-3, caspase-7, and VEGF levels were quantified.

Main Results:

  • Ramucirumab decreased Caco-2 cell viability (IC50 = 780 µg/ml) and increased LDH release.
  • Apoptosis significantly increased, with cell cycle arrest observed primarily in the S-phase.
  • Mitochondrial dysfunction (decreased ΔΨm), elevated ROS, and increased VEGF were noted.
  • Caspase-3 and caspase-7 activation indicated caspase-mediated apoptosis.

Conclusions:

  • Ramucirumab exhibits anti-cancer activity against Caco-2 cells by inducing cell cycle arrest and apoptosis.
  • The mechanism involves mitochondrial dysfunction and activation of the caspase pathway.
  • These findings suggest broader anti-tumor potential for ramucirumab beyond its anti-angiogenic properties.
Keywords:
Caco-2 cellsanti-angiogenesisapoptosiscaspase activationramucirumab

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