Sorghum Phenolics Demonstrate Estrogenic Action and Induce Apoptosis in Nonmalignant Colonocytes

Abstract

Evidence indicates sorghum may be protective against colon cancer; however, the mechanisms are unknown. Estrogen is believed to protect against colon cancer development by inducing apoptosis in damaged nonmalignant colonocytes. Three sorghum extracts (white, red, and black) were screened for estrogenic activity using cell models expressing estrogen receptor α (ER-α; MCF-7 breast cancer cells) and β [ER-β; nonmalignant young adult mouse colonocytes (YAMC)]. Black and white sorghum extracts had significant estrogenic activity mediated through both estrogen receptors at 1-5 and 5-10 μg/mL, respectively; but red sorghum did not. Activation of ER-β in YAMC reduced cell growth via induction of apoptosis. Only the black and red sorghums contained 3-deoxyanthocyanins; however, these compounds were non-estrogenic. Flavones with estrogenic properties, luteolin (0.41-2.12 mg/g) and apigenin (1.1-1.4 mg/g), and their O-methyl derivatives (0.70-0.95 mg/g) were detected in white and black sorghums, but not in the red sorghum. On the other hand, naringenin, a flavanone known to interfere with transcriptional activities of estrogen, was only detected in the red sorghum extract (as its 7-O-glycoside) at relatively high concentration (11.8 mg/g). Sorghum flavonoid composition has important implications on possible modes of chemoprotection by sorghum against colon carcinogenesis.

Sorghum Grain: From Genotype, Nutrition, and Phenolic Profile to Its Health Benefits and Food Applications

“…They are often conjugated with monomeric carbohydrate and glycerol and exist in the free form as esters (conjugated) or aldehydes (unconjugated). The ester conjugates are the primary extractable phenolic acids in sorghum (Dykes & Rooney, ; Svensson, Sekwati‐Monang, Lutz, Schieber, & Gänzle, ; Yang, Allred, Geera, Allred, & Awika, ).…”

“…Most of the phenolic acids (about 70% to 95%) in sorghum are in the bound form. Among them, ferulic acid (100 to 500 µg/g in the grain) is the most abundant one and can account for up to 90% of the total bound phenolic acids (Chiremba, Taylor, Rooney, & Beta, ; Yang et al., ). The bound phenolic acids have low bioavailability, because of the extensive covalent bonds that are resistant to enzymatic digestion (Saura‐Calixto, ).…”

“…The flavone content (Figure D; Table ) in sorghum grain is about 20 to 390 µg/g, relatively low compared to other flavonoids (Girard & Awika, ). Some flavonoids exist naturally in the form of glycosides such as luteolin, but others like apigenin exist mainly as aglycone forms (Yang et al., ; Yang, Allred, Dykes, Allred, & Awika, ). The glycosides in sorghum are predominant O‐glycosides and are very unstable in acidic environments, because the glycosidic bonds are readily hydrolyzable and form the aglycones; the aglycone forms of luteolin and apigenin are the dominant flavones in sorghum (Dykes et al., ; Yang et al., ).…”

Sorghum: An Underutilized Cereal Whole Grain with the Potential to Assist in the Prevention of Chronic Disease

“…Powerful anti-proliferative effects were also observed against colon cancer cells when black, red, and white sorghum extracts, rich in 3-DA were tested. (104,105) Yang et al (106) proposed that these protective effects result from estrogen-induced apoptosis of the non-malignant colonocytes that were strongly influenced by the flavones, apigenin and luteolin. In breast cancer cell lines, 3-DA isolated from red sorghum bran have been shown to have strong anti-proliferative properties and to be cytotoxic.…”

Efeito do déficit hí­drico e CO₂ elevado sobre substâncias fenólicas e ligninas do sorgo var. 'BRS 330'

“…Certas variedades de sorgo podem conter elevadas concentrações de flavanonas. Por exemplo, verificou-se que uma variedade de sorgo vermelho contém 11,8 mg/g (base seca), de naringenina (Yang et al, 2012).…”