Tumor Biology

, Volume 35, Issue 10, pp 10159–10167 | Cite as

Verrucarin A alters cell-cycle regulatory proteins and induces apoptosis through reactive oxygen species-dependent p38MAPK activation in the human breast cancer cell line MCF-7

  • Kandasamy Palanivel
  • Veerasamy Kanimozhi
  • Balamuthu Kadalmani
Research Article


Verrucarin A (VA), an active constituent of pathogenic fungus Myrothecium verrucaria, which has the ability to inhibit the growth of breast cancer cells. However, the mechanism by which VA exerts its inhibitory potential remains elusive. Here, we demonstrated that VA inhibited the growth of MCF-7 breast cancer cells, increased the levels of reactive oxygen species (ROS), and subsequently induced mitochondrial membrane potential (Δψm) loss, leading to the increase of Bax/Bcl-2 ratio, cytochrome c release, caspase activation, PARP degradation, and apoptosis. VA effectively increased the phosphorylation of p38MAPK and diminished the phosphorylation of ERK/Akt. In addition, VA caused cell cycle deregulation through the induction of p21 and p53. Furthermore, ROS scavenger (n-acetyl-l-cysteine) and p38MAPK inhibitor (SB202190) effectively abrogated the VA-induced cell cycle deregulation and apoptosis. Conversely, U0126, an ERK1/2 inhibitor, enhanced the VA-induced apoptotic signals. Taken together, our results suggest that VA-induces apoptosis and cell cycle deregulation in MCF-7 cells through ROS-dependent p38MAPK activation.


Apoptosis Cancer Cell cycle deregulation MAPK ROS Verrucarin A 



This study was supported by University Grants Commission, India, under the Special Assistance Programme (UGC–SAP)-Research Fellowship for Meritorious Students in Science (RFMS).

Conflicts of interest



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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Kandasamy Palanivel
    • 1
  • Veerasamy Kanimozhi
    • 1
  • Balamuthu Kadalmani
    • 1
  1. 1.Department of Animal ScienceBharathidasan UniversityTiruchirappalliIndia

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