PMID- 25553799 OWN - NLM STAT- MEDLINE DCOM- 20160211 LR - 20150312 IS - 2042-650X (Electronic) IS - 2042-6496 (Linking) VI - 6 IP - 3 DP - 2015 Mar TI - Enhanced action of apigenin and naringenin combination on estrogen receptor activation in non-malignant colonocytes: implications on sorghum-derived phytoestrogens. PG - 749-55 LID - 10.1039/c4fo00300d [doi] AB - Activation of estrogen receptor-beta (ERbeta) is an important mechanism for colon cancer prevention. Specific sorghum varieties that contain flavones were shown to activate ER in non-malignant colonocytes at low concentrations. This study aimed to determine positive interactions among estrogenic flavonoids most relevant in sorghum. Apigenin and naringenin were tested separately and in combination for their ability to influence ER-mediated cell growth in non-malignant young adult mouse colonocytes (YAMC). Sorghum extracts high in specific flavanones and flavones were also tested. Apigenin reduced ER-mediated YAMC cell growth comparable to physiological levels of estradiol (E(2), 1 nM) at 1 muM; naringenin had similar effect at 10 muM. However, when combined, 0.1 muM apigenin plus 0.05 muM naringenin produced similar effect as 1 nM E(2); these concentrations represented 1/10th and 1/200th, respectively, of the active concentrations of apigenin and naringenin, demonstrating a strong enhanced action. A sorghum extract higher in flavones (apigenin and luteolin) (4.8 mg g(-1)) was more effective (5 mug mL(-1)) at activating ER in YAMC than a higher flavanone (naringenin and eriodictyol) (28.1 mg g(-1)) sorghum extract (10 mug mL(-1)). Enhanced actions observed for apigenin and naringenin were adequate to explain the level of effects produced by the high flavone and flavanone sorghum extracts. Strong positive interactions among sorghum flavonoids may enhance their ability to contribute to colon cancer prevention beyond what can be modeled using target compounds in isolation. FAU - Yang, Liyi AU - Yang L AD - Cereal Quality Laboratory, Soil & Crop Science Department, Texas A&M University, College Station, Texas, USA. jawika@ag.tamu.edu. FAU - Allred, Kimberly F AU - Allred KF FAU - Dykes, Linda AU - Dykes L FAU - Allred, Clinton D AU - Allred CD FAU - Awika, Joseph M AU - Awika JM LA - eng PT - Comparative Study PT - Journal Article PL - England TA - Food Funct JT - Food & function JID - 101549033 RN - 0 (Anticarcinogenic Agents) RN - 0 (Estrogen Receptor Antagonists) RN - 0 (Estrogen Receptor beta) RN - 0 (Flavanones) RN - 0 (Phytoestrogens) RN - 0 (Pigments, Biological) RN - 0 (Plant Extracts) RN - 7V515PI7F6 (Apigenin) RN - HN5425SBF2 (naringenin) RN - KUX1ZNC9J2 (Luteolin) RN - Q520486B8Y (eriodictyol) SB - IM MH - Animals MH - Anticarcinogenic Agents/analysis/chemistry/isolation & purification/*pharmacology MH - Apigenin/agonists/chemistry/isolation & purification/*pharmacology MH - Cell Line MH - Cell Proliferation/drug effects MH - Colon/*drug effects/metabolism MH - Colonic Neoplasms/metabolism/prevention & control MH - Drug Synergism MH - Estrogen Receptor Antagonists/pharmacology MH - Estrogen Receptor beta/agonists/antagonists & inhibitors/metabolism MH - Flavanones/agonists/analysis/chemistry/isolation & purification/*pharmacology MH - Functional Food/analysis MH - Intestinal Mucosa/*drug effects/metabolism MH - Luteolin/analysis/isolation & purification/pharmacology MH - Mice MH - Osmolar Concentration MH - Phytoestrogens/agonists/chemistry/isolation & purification/*pharmacology MH - Pigments, Biological/biosynthesis MH - Plant Extracts/chemistry/isolation & purification/pharmacology MH - Seeds/chemistry/metabolism MH - Sorghum/*chemistry/metabolism EDAT- 2015/01/03 06:00 MHDA- 2016/02/13 06:00 CRDT- 2015/01/03 06:00 PHST- 2015/01/03 06:00 [entrez] PHST- 2015/01/03 06:00 [pubmed] PHST- 2016/02/13 06:00 [medline] AID - 10.1039/c4fo00300d [doi] PST - ppublish SO - Food Funct. 2015 Mar;6(3):749-55. doi: 10.1039/c4fo00300d.