Anticancer Activity of a Novel High Phenolic Sorghum Bran in Human Colon Cancer Cells
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
Authors: Lee, Seong-Ho; Lee, Jihye; Herald, Thomas; Cox, Sarah; Noronha, Leela; Perumal, Ramasamy; Lee, Hee-Seop; Smolensky, Dmitriy
Human colon cancer is the third leading cause of mortality in the United States and worldwide. Chemoprevention using diet is widely accepted as a promising approach for cancer management. Numerous population studies indicate a negative correlation between the incidence of colon cancer and consumption of whole grains with a high content of bioactive phenolic compounds. In the current study, we evaluated the anticancer properties of a high phenolic sorghum bran extract prepared using 70% ethanol with 5% citric acid solvent at room temperature. A significant dose-dependent suppression of cell proliferation was observed in human colon cancer cells treated with the high phenolic sorghum bran extract. Apoptosis and S phase growth arrest were induced, while cell migration and invasion were inhibited by this treatment; these effects were accompanied by altered expression of apoptosis, cell cycle, and metastasis-regulating genes. We also found that the high phenolic sorghum bran extract stimulated DNA damage in association with induction of extracellular signal-regulated kinase (ERK) and c-Jun-NH2-terminal kinase (JNK) and subsequent expression of activating transcription factor 3 (ATF3). The present study expands our understanding of the potential use of high phenolic sorghum bran to prevent human colon cancer.
Thrombospondin-1 Mediates Axon Regeneration in Retinal Ganglion Cells
Authors: Bray, Eric R.; Yungher, Benjamin J.; Levay, Konstantin; Ribeiro, Marcio; Dvoryanchikov, Gennady; Ayupe, Ana C.; Thakor, Kinjal; Marks, Victoria; Randolph, Michael; Danzi, Matt C.; Schmidt, Tiffany M.; Chaudhari, Nirupa; Lemmon, Vance P.; Hattar, Samer; Park, Kevin K.
Neuronal subtypes show diverse injury responses, but the molecular underpinnings remain elusive. Using transgenic mice that allow reliable visualization of axonal fate, we demonstrate that intrinsically photo-sensitive retinal ganglion cells (ipRGCs) are both resilient to cell death and highly regenerative. Using RNA sequencing (RNA-seq), we show genes that are differentially expressed in ipRGCs and that associate with their survival and axon regeneration. Strikingly, thrombospondin-1 (Thbs1) ranked as the most differentially expressed gene, along with the well-documented injury-response genes Atf3 and Jun. THBS1 knockdown in RGCs eliminated axon regeneration. Conversely, RGC overexpression of THBS1 enhanced regeneration in both ipRGCs and non-ipRGCs, an effect that was dependent on syndecan- 1, a known THBS1-binding protein. All structural domains of the THBS1 were not equally effective; the trimerization and C-terminal domains promoted regeneration, while the THBS type-1 repeats were dispensable. Our results identify cell-type-specific induction of Thbs1 as a novel gene conferring high regenerative capacity.