| Sorghum bicolor is the fifth most cultivated cereal crop worldwide. Varieties of S bicolor, known as grain sorghum, are cultivated for human food and animal feed. Certain varieties, known as sweet sorghum, concentrate sugar in the pith cells of the stalk and are cultivated for sugars and syrups. Recently, interest has grown in the use of sweet sorghum as a feedstock for biofuel production. This is due to reduced water requirements, shorter growing periods and reduced cultivation cost when compared to other feedstocks. Biofuel production of sweet sorghum generates large masses of biological wastes, comprised of stalks, leaves, leaf sheaths and seed heads. This biomass could serve as a potential reservoir for bioactive compounds for human health. Rich in phenolic acids and flavonoids, these parts of the sorghum plant have been used as a traditional medicine in African and Asian cultures for the treatment of various disease states, including cancer. Furthermore, recent studies have elucidated in vitro and in vivo antiinflammatory, antioxidant, and anticancer activities of the seed head, leaf and leaf sheath. Much less is known about the in vitro and in vivo bioactivities of the stalk components of sweet sorghum varieties. Here, the in vitro anticancer activity, and the in vivo antiinflammatory and antioxidant activity of sweet sorghum with a focus on the dermal layer, a component of sweet sorghum stalk, were investigated. It was hypothesized that the dermal layer contains phenolic compounds with antiproliferative, proapoptotic and antiinflammatory/antioxidant properties. Given the high rates of cancer incidence and mortality, as well as the close connection to a Western diet, in vitro colon cancer cell models and in vivo Western diet induced obesity and oxidative stress models were utilized for the purposes of this study.;For in vitro studies, the colon cancer HCT116 cell line and colon cancer stem cells (CCSCs), and their p53 variants HCT116 p53 -/- and CCSCs p53 shRNA, were treated with different doses of phenolic rich extracts from the stalk components (pith and dermal layer), the leaves, and the seed head. Phenolic compounds are ubiquitous throughout the plant kingdom, consistently display bioactivity, and their antioxidant activity has been linked to the anticancer activity of phenolics. Total phenolics and antioxidant activities were determined by the Folin-Ciocalteu and 2,2`-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) assays, respectively. Individual phenolic compounds were identified by LC-MS analysis. Increased proliferation and suppressed apoptosis are two important hallmarks of cancer and are commonly targets of anticancer therapies. Given this, cancer cell proliferation was assessed with cell counting and BrdU assay, and apoptosis was assessed by Caspase 3/7 Glo, PARP cleavage and TUNEL assays. The colony formation assay was used as a measure of cell stemness in CCSCs.;For in vivo studies of inflammation and oxidative stress, the murine Western/high-fat diet (HFD; 40% kcal fat) induced obesity and oxidative stress model was utilized. Male and female A/J mice were provided with HFD and low-fat diet control (LFD) for 10 weeks with and without 1% sweet sorghum stalk (dermal layer) extract (SS). During the treatment period, weekly measures of bodyweight, feed intake and water intake were collected. At the end of the study, dual energy X-ray absorptiometry (DEXA) was performed to assess adiposity. After treatment period, mice were sacrificed, vital organs weighed, and tissues and plasma collected for further analysis.;It was demonstrated that the stalk (pith and dermal layer), leaf, and seed head contain phenolic and antioxidant compounds conferring anticancer properties in colon cancer stem cells, supporting the hypothesis. This activity was most prominent in the dermal layer and seed head. Furthermore these extracts were shown to act via decreasing beta-catenin and beta-catenin's prosurvival target genes. Additionally, we have demonstrated phenolic rich extract from dermal has in vivo antioxidant activities, and was well-tolerated in a high-fat diet mouse model of obesity and oxidative stress. More research is still needed to further elucidate the mechanisms through which sweet sorghum derived bioactive compounds favorably alter beta-catenin levels in vitro and oxidative stress in vivo. Together this data suggests that sweet sorghum, an attractive source of fermentable sugars for biofuel production producing large quantities of biomass, is also an attractive reservoir of bioactive phenolic compounds with human health benefiting properties. (Abstract shortened by UMI.). |
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