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Tumor Biology

, Volume 37, Issue 8, pp 10517–10531 | Cite as

Marine steroid derived from Acropora formosa enhances mitochondrial-mediated apoptosis in non-small cell lung cancer cells

  • Ramalingam Vaikundamoorthy
  • Revathidevi Sundaramoorthy
  • Varunkumar Krishnamoorthy
  • Ravikumar Vilwanathan
  • Rajaram Rajendran
Original Article

Abstract

p53 pathway has been revealed to mediate cellular stress responses and trigger DNA repair, cell cycle arrest, senescence, and apoptosis. We isolated 2-ethoxycarbonyl-2-β-hydroxy-A-nor-cholest-5-ene-4one (ECHC) from butanol extracts of scleractinian coral Acropora formosa and reported its potential antioxidant and antimicrobial activity as well as less toxicity against zebrafish Danio rerio. In the present study, we intend to explore p53-mediated apoptosis pathway enhanced by ECHC in A549 human non-small cell lung cancer cell lines. This report shows that ECHC increases ROS generation and sensitizes mitochondrial membrane that leads to the release of cytochrome C (Cyto C) into cytosol. Further, ECHC decreases the expression of antiapoptotic genes such as TNF-α, IL-8, Bcl2, MMP2, and MMP9 which are actively involved in cancer cell proliferation, invasion, and metastasis etc. It also increases the expression of apoptotic genes Cyto C, Bax, and p21, which are responsible for cell cycle arrest and cell death. The tumor suppressor p53 was also observed to be upregulated during ECHC treatment in untransformed cells and was more likely to result in cell cycle arrest, senescence, and apoptosis. Finally, ECHC also down regulates the expression of caspase-9 and caspase-3 which are the death stage of intrinsic apoptosis. Our findings suggested that ECHC enhances ROS generation and mitochondrial sensitization determines the threshold for irreversible p53-mediated intrinsic apoptosis pathway.

Keywords

Acropora formosa ECHC A549 cells Apoptosis p53 Caspase 

Notes

Acknowledgment

The author acknowledges the authorities of Bharathidasan University for providing the facilities to carry out this work. The author also acknowledges the Chair Person, School of Biological Sciences, Madurai Kamaraj University, Madurai, India for providing the facilities for cell cycle analysis.

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  • Ramalingam Vaikundamoorthy
    • 1
  • Revathidevi Sundaramoorthy
    • 2
  • Varunkumar Krishnamoorthy
    • 3
  • Ravikumar Vilwanathan
    • 3
  • Rajaram Rajendran
    • 1
  1. 1.DNA Barcoding and Marine Genomics Lab, Department of Marine ScienceBharathidasan UniversityTiruchirappalliIndia
  2. 2.Department of Genetics, Institute of Basic Medical SciencesMadras University, Taramani CampusChennaiIndia
  3. 3.Cancer Biology Lab, Department of BiochemistryBharathidasan UniversityTiruchirappalliIndia

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