title: p-HPEA-EDA, a phenolic compound of virgin olive oil, activates AMP-activated protein kinase to inhibit carcinogenesis.
abstract: Phenolic constituents of virgin olive oil are reported to have antitumor activity. However, the underlying molecular mechanisms and specific target proteins of virgin olive oil remain to be elucidated. Here, we report that dialdehydic form of decarboxymethyl ligstroside aglycone (p-HPEA-EDA), a phenolic compound of virgin olive oil, inhibits tumor promoter-induced cell transformation in JB6 Cl41 cells and suppress cyclooxygenase-2 (COX-2) and tumorigenicity by adenosine monophosphate-activated protein kinase (AMPK) activation in HT-29 cells. p-HPEA-EDA inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced phosphorylation of extracellular signal-regulated kinases 1/2 and p90RSK in JB6 Cl41 cells, resulting in the inhibition of cell proliferation, activator protein-1 transactivation and cell transformation promoted by TPA. Moreover, p-HPEA-EDA strongly inhibited the cell viability and COX-2 expression by activation of AMPK activity in HT-29 cells, resulted from depletion of intracellular adenosine triphosphate. p-HPEA-EDA-induced activation of caspase-3 and poly-adenosine diphosphate-ribose polymerase, phosphorylation of p53 (Ser15) and DNA fragmentation in HT-29 cells, leading to apoptosis. Importantly, p-HPEA-EDA suppressed the colony formation of HT-29 cells in soft agar. In contrast, Compound C, an AMPK inhibitor, and Z-DEVD-FMK, a caspase-3 inhibitor, blocked the p-HPEA-EDA-inhibited colony formation in HT-29 cells. In vivo chorioallantoic membrane assay also showed that p-HPEA-EDA-inhibited tumorigenicity of HT-29 cells. These findings revealed that targeted activation of AMPK and inhibition of COX-2 expression by p-HPEA-EDA contribute to the chemopreventive and chemotherapeutic potential of virgin olive oil against colon cancer cells.
authors.affiliation: BK21 Project Team, College of Pharmacy, Department of Pathology, School of Dentistry, Chosun University, Gwangju 501-759, Republic of Korea.
authors.forename: Prem
authors.initials: P
authors.lastname: Khanal
authors.forename: Won-Keun
authors.initials: WK
authors.lastname: Oh
authors.forename: Hyo Jeong
authors.initials: HJ
authors.lastname: Yun
authors.forename: Gwang Mo
authors.initials: GM
authors.lastname: Namgoong
authors.forename: Sang-Gun
authors.initials: SG
authors.lastname: Ahn
authors.forename: Seong-Min
authors.initials: SM
authors.lastname: Kwon
authors.forename: Hoo-Kyun
authors.initials: HK
authors.lastname: Choi
authors.forename: Hong Seok
authors.initials: HS
authors.lastname: Choi
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000447:Aldehydes / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D051546:Cyclooxygenase 2 / Q000032:analysis; D000081004:Cyclopentane Monoterpenes; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D000069463:Olive Oil; D010636:Phenols / Q000494:pharmacology*; D010938:Plant Oils / Q000737:chemistry*; D013755:Tetradecanoylphorbol Acetate; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000447:Aldehydes; D000970:Antineoplastic Agents; D000081004:Cyclopentane Monoterpenes; D000069463:Olive Oil; D010636:Phenols; D010938:Plant Oils; D016159:Tumor Suppressor Protein p53; C503534:oleocanthal; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D055372:AMP-Activated Protein Kinases; D013755:Tetradecanoylphorbol Acetate