Olive oil enriched diet suppresses hepatocellular carcinoma (HCC) tumor growth via focal adhesion pathway

Objective: Olive oil, an integral ingredient of the Mediterranean diet, has been suggested to have a potential role in lowering risk of several cancers. However, there is a lack of literature reporting the detailed mechanism of dietary olive oil on HCC. In this present study, we examine the effects of olive oil enriched diet on the genetic profile changes and the relation to malignancy and metastasis of HCC. Methodology: Human low metastatic hepatocellular carcinoma cell line (MHCC97L) was used in the orthotopic xenograft model. We analyzed the gene expression profile of HCC tumor implanted in nude mice, either fed with normal rat chow (n = 3) or 20% olive oil enriched diet (n = 3), by performing Affymetrix microarray analysis. Results: Tumor volume of nude mice fed with 20% olive oil diet was significantly reduced by 80%. Our microarray data showed that the molecular mechanism of HCC tumor growth suppression could be explained by focal adhesion pathway, which is particularly associated with cell migration and integrin signaling. The present study revealed olive oil-enriched diet down-regulated the genes expression of extracellular matrix (ECM)-linked focal adhesion pathway candidates, like ECM and protein kinase, alpha (PKCA), and insulin-like growth factor 1 (IGF-1)-linked focal adhesion pathway genes, such as met proto-oncogene (MET). In addition, the up-regulation of the c-Jun N-terminal Kinase (JNK) candidates, such as cell division cycle 42 (cdc42, GTP-binding protein), mitogen-activated protein kinase / extracellular signal regulated kinase kinase 1 (MEKK1) and mitogen-activated protein kinase kinase 7 (MKK7), by olive oil-enriched diet might contributed to the onset of apoptosis or cell cycle delay. Certainly, an appropriate study of the active component(s) in olive oil on HCC must be carried out to provide stronger evidence to a new molecular approach of diet intervention in the management of HCC