1. Comparative Cytotoxic Activity of Hydroxytyrosol and Its Semisynthetic Lipophilic Derivatives in Prostate Cancer Cells
- Author
-
Enrique Gómez-Gómez, Justo P. Castaño, Antonio J. Montero-Hidalgo, Vicente Herrero-Aguayo, Juan M. Jiménez-Vacas, Raúl M. Luque, Prudencio Sáez-Martínez, Andrés Madrona, Manuel D. Gahete, José L. Espartero, Antonio J. León-González, Universidad de Sevilla. Departamento de Química Orgánica y Farmacéutica, Universidad de Sevilla. Departamento de Farmacología, [León-González,AJ, Sáez-Martínez,P, Jiménez-Vacas,JM, Herrero-Aguayo,V, Montero-Hidalgo,AJ, Gómez-Gómez,E, Castaño,JP, Gahete,MD, Luque,RM] Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), Cordoba, Spain. [León-González,AJ, Luque,RM] Department of Cell Biology, Physiology and Immunology, University of Cordoba, Cordoba, Spain. [León-González,AJ, Luque,RM] Reina Sofia University Hospital (HURS), Cordoba, Spain. [León-González,AJ, Luque,RM] CIBER Physiopathology of Obesity and Nutrition (CIBERobn), Cordoba, Spain. [[León-González,AJ] Department of Pharmacology, Faculty of Pharmacy, University of Seville, Seville, Spain. [Gómez-Gómez,E] Urology Service, HURS/IMIBIC, Cordoba, Spain. [Madrona,A, Espartero,JL] Department of Organic and Pharmaceutical Chemistry, Faculty of Pharmacy, University of Seville, Seville, Spain., and This research was funded by Junta de Andalucía (PI-0152-2019, BIO-0139, RH-0084-2020), MINECO/MECD (PID2019-105564RB-I00, PID2019-105201RB-I00, FPU17/00263, FPU16/06190, FPU18/02485), University of Córdoba (Programa Operativo FEDER Andalucía: 27416), Instituto de Salud Carlos III, co-funded by European Union (ERDF/ESF, 'Investing in your future') [PI20/01301, CD16/00092], and CIBERobn. CIBER is an initiative of Instituto de Salud Carlos III, Ministerio de Sanidad, Servicios Sociales e Igualdad, Spain.
- Subjects
Neoplasias de la próstata ,Carcinogenesis ,Physiology ,Clinical Biochemistry ,Pharmacology ,medicine.disease_cause ,Biochemistry ,Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Movement [Medical Subject Headings] ,Semisynthetic derivatives ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] ,chemistry.chemical_compound ,Chemicals and Drugs::Complex Mixtures::Waste Products::Waste Water [Medical Subject Headings] ,Extra virgin olive oil ,Cytotoxic T cell ,Hydroxytyrosol ,Phosphorylation ,Phenomena and Processes::Metabolic Phenomena::Metabolism::Phosphorylation [Medical Subject Headings] ,Cell proliferation ,Prostate cancer ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Nutrition Therapy::Diet Therapy::Diet, Mediterranean [Medical Subject Headings] ,semisynthetic derivatives ,Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::Signal Transduction [Medical Subject Headings] ,Células PC-3 ,Diseases::Neoplasms::Neoplastic Processes::Carcinogenesis [Medical Subject Headings] ,prostate cancer ,Aceite de oliva ,Diseases::Male Urogenital Diseases::Urogenital Neoplasms::Genital Neoplasms, Male::Prostatic Neoplasms [Medical Subject Headings] ,Anticancer ,Phenomena and Processes::Biological Phenomena::Biological Processes::Regeneration::Wound Healing [Medical Subject Headings] ,Fosforilación ,hydroxytyrosol ,Carcinogénesis ,Proliferación celular ,Check Tags::Male [Medical Subject Headings] ,RM1-950 ,anticancer ,Article ,extra virgin olive oil ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Vital Statistics::Morbidity::Incidence [Medical Subject Headings] ,Mediterranean diet ,LNCaP ,medicine ,PC-3 cells ,Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Growth Processes::Cell Proliferation [Medical Subject Headings] ,Molecular Biology ,Protein kinase B ,Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Phosphotransferases (Alcohol Group Acceptor)::Protein Kinases::Protein-Serine-Threonine Kinases::Proto-Oncogene Proteins c-akt [Medical Subject Headings] ,AKT ,Chemicals and Drugs::Organic Chemicals::Ethers [Medical Subject Headings] ,Cancer ,Cell Biology ,medicine.disease ,Dieta mediterránea ,In vitro ,chemistry ,Cell culture ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Chemistry Techniques, Analytical::Electrophoresis::Blotting, Western [Medical Subject Headings] ,Therapeutics. Pharmacology - Abstract
A high adherence to a Mediterranean diet has been related to numerous beneficial effects in human health, including a lower incidence and mortality of prostate cancer (PCa). Olive oil is an important source of phenolic bioactive compounds, mainly hydroxytyrosol (HT), of this diet. Be-cause of the growing interest of this compound and its derivatives as a cancer chemopreventive agent, we aimed to compare the in vitro effect of HT isolated from olive mill wastewaters and five semisynthetic alkyl ether, ester, and nitro-derivatives against prostate cancer (PCa) cell lines. The effect in cell proliferation was determined in RWPE-1, LNCaP, 22Rv1, and PC-3 cells by resazurin assay, the effect in cell migration by wound healing assay, and tumorsphere and colony formation were evaluated. The changes in key signaling pathways involved in carcinogenesis were assessed by using a phosphorylation pathway profiling array and by Western blotting. Antiproliferative effects of HT and two lipophilic derivatives [hydroxytyrosyl acetate (HT-Ac)/ethyl hydroxytyrosyl ether (HT-Et)] were significantly higher in cancerous PC-3 and 22Rv1 cells than in non-malignant RWPE-1 cells. HT/HT-Ac/HT-Et significantly reduced migration capacity in RWPE-1 and PC-3 and prostatosphere size and colony formation in 22Rv1, whereas only HT-Ac and HT-Et reduced these functional parameters in PC-3. The cytotoxic effect in 22Rv1 cells was correlated with modifications in the phosphorylation pattern of key proteins, including ERK1/2 and AKT. Consistently, HT-Ac and HT-Et decreased p-AKT levels in PC-3. In sum, our results suggest that HT and its lipophilic derivatives could be considered as potential therapeutic tools in PCa. Junta de Andalucía PI-0152-2019, BIO-0139, RH-0084-2020 Ministerio de Economía y Competitividad PID2019-105564RB-I00, PID2019-105201RB-I00, FPU17/00263, FPU16/06190, FPU18/02485
- Published
- 2021