Oleocanthal exerts antitumor effects on human liver and colon cancer cells through ROS generation

Cusimano,Antonella; Balasus,Daniele; Azzolina,Antonina; Augello,Giuseppa; Emma,Maria R.; Di Sano,Caterina; Gramignoli,Roberto; Strom,Stephen C.; McCubrey,James A.; Montalto,Giuseppe; Cervello,Melchiorre

doi:10.3892/ijo.2017.4049

Oleocanthal exerts antitumor effects on human liver and colon cancer cells through ROS generation

Authors:
- Antonella Cusimano
- Daniele Balasus
- Antonina Azzolina
- Giuseppa Augello
- Maria R. Emma
- Caterina Di Sano
- Roberto Gramignoli
- Stephen C. Strom
- James A. McCubrey
- Giuseppe Montalto
- Melchiorre Cervello
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Affiliations: Institute of Biomedicine and Molecular Immunology ‘Alberto Monroy’, National Research Council (CNR), Palermo, Italy, Division of Pathology, Department of Laboratory Medicine, Cell Transplantation and Regenerative Medicine, Karolinska Institutet, Stockholm, Sweden, Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, NC, USA
Published online on: June 21, 2017 https://doi.org/10.3892/ijo.2017.4049
Pages: 533-544

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Abstract

The beneficial health properties of the Mediterranean diet are well recognized. The principle source of fat in Mediterranean diet is extra-virgin olive oil (EVOO). Oleocanthal (OC) is a naturally occurring minor phenolic compound isolated from EVOO, which has shown a potent anti-inflammatory activity, by means of its ability to inhibit the cyclooxygenase (COX) enzymes COX-1 and COX-2. A large body of evidence indicates that phenols exhibit anticancer activities. The aim of the present study was to evaluate the potential anticancer effects of OC in hepatocellular carcinoma (HCC) and colorectal carcinoma (CRC) models. A panel of human HCC (HepG2, Huh7, Hep3B and PLC/PRF/5) and CRC (HT29, SW480) cell lines was used. Cells were treated with OC, and cell viability and apoptosis were evaluated. Compared with classical commercially available COX inhibitors (ibuprofen, indomethacin, nimesulide), OC was more effective in inducing cell growth inhibition in HCC and CRC cells. Moreover, OC inhibited colony formation and induced apoptosis, as confirmed by PARP cleavage, activation of caspases 3/7 and chromatin condensation. OC treatment in a dose dependent-manner induced expression of γH2AX, a marker of DNA damage, increased intracellular ROS production and caused mitochondrial depolarization. Moreover, the effects of OC were suppressed by the ROS scavenger N-acetyl-L-cysteine. Finally, OC was not toxic in primary normal human hepatocytes. In conclusion, OC treatment was found to exert a potent anticancer activity against HCC and CRC cells. Taken together, our findings provide preclinical support of the chemotherapeutic potential of EVOO against cancer.

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