title: The anti-cancer effects of carotenoids and other phytonutrients resides in their combined activity.
abstract: Epidemiological studies have consistently shown that regular consumption of fruits and vegetables is strongly associated with reduced risk of developing chronic diseases, such as cancer. It is now accepted that the actions of any specific phytonutrient alone do not explain the observed health benefits of diets rich in fruits and vegetables as nutrients that were taken alone in clinical trials did not show consistent preventive effects. The considerable cost and complexity of such clinical trials requires prudent selection of combinations of ingredients rather than single compounds. Indeed, synergistic inhibition of prostate and mammary cancer cell growth was evident when using combinations of low concentrations of various carotenoids or carotenoids with retinoic acid and the active metabolite of vitamin-D. In this study we aimed to develop simple and sensitive in vitro methods which provide information on potent combinations suitable for inclusion in clinical studies for cancer prevention. We, thus, used reporter gene assays of the transcriptional activity of the androgen receptor in hormone-dependent prostate cancer cells and of the electrophile/antioxidant response element (EpRE/ARE) transcription system. We found that combinations of several carotenoids (e.g., lycopene, phytoene and phytofluene), or carotenoids and polyphenols (e.g., carnosic acid and curcumin) and/or other compounds (e.g., vitamin E) synergistically inhibit the androgen receptor activity and activate the EpRE/ARE system. The activation of EpRE/ARE was up to four fold higher than the sum of the activities of the single ingredients, a robust hallmark of synergy. Such combinations can further be tested in the more complex in vivo models and human studies.
authors.affiliation: Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev and Soroka Medical Center, Beer Sheva, Israel.
authors.forename: Karin
authors.initials: K
authors.lastname: Linnewiel-Hermoni
authors.affiliation: Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev and Soroka Medical Center, Beer Sheva, Israel.
authors.forename: Marina
authors.initials: M
authors.lastname: Khanin
authors.affiliation: Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev and Soroka Medical Center, Beer Sheva, Israel.
authors.forename: Michael
authors.initials: M
authors.lastname: Danilenko
authors.affiliation: Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev and Soroka Medical Center, Beer Sheva, Israel.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Zango
authors.affiliation: Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev and Soroka Medical Center, Beer Sheva, Israel.
authors.forename: Yaara
authors.initials: Y
authors.lastname: Amosi
authors.affiliation: Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev and Soroka Medical Center, Beer Sheva, Israel.
authors.forename: Joseph
authors.initials: J
authors.lastname: Levy
authors.affiliation: Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev and Soroka Medical Center, Beer Sheva, Israel. Electronic address: yoav@bgu.ac.il.
authors.forename: Yoav
authors.initials: Y
authors.lastname: Sharoni
mesh_terms: D000728:Androgens / Q000235:genetics / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000378:metabolism; D002338:Carotenoids / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004357:Drug Synergism; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology; D006801:Humans; D000077276:Lycopene; D008297:Male; D064209:Phytochemicals / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000473:pathology; D020218:Response Elements / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D000728:Androgens; D000970:Antineoplastic Agents; D000975:Antioxidants; D015525:Fatty Acids, Omega-3; D064209:Phytochemicals; D002338:Carotenoids; D000077276:Lycopene
keywords: Androgen signaling; Carotenoids; Polyphenols; Prostate cancer; Synergy