Indole-3-Carbinol: Occurrence, Health-Beneficial Properties, and Cellular/Molecular Mechanisms.

Indole-3-carbinol (I3C) is a bioactive phytochemical abundant in cruciferous vegetables. One of its main in vivo metabolites is 3,3'-diindolylmethane (DIM), formed by the condensation of two molecules of I3C. Both I3C and DIM alter multiple signaling pathways and related molecules controlling diverse cellular events, including oxidation, inflammation, proliferation, differentiation, apoptosis, angiogenesis, and immunity. There is a growing body of evidence from both in vitro and in vivo models that these compounds possess strong potential to prevent several forms of chronic disease such as inflammation, obesity, diabetes, cardiovascular disease, cancer, hypertension, neurodegenerative diseases, and osteoporosis. This article reviews current knowledge of the occurrence of I3C in nature and foods, along with the beneficial effects of I3C and DIM concerning prevention and treatment of human chronic diseases, focusing on preclinical studies and their mechanisms of action at cellular and molecular levels.

Pendimethalin induces apoptotic cell death through activating ER stress-mediated mitochondrial dysfunction in human umbilical vein endothelial cells.

Pendimethalin is globally registered for control of a wide range of weeds in agriculture and home landscaping. Human exposure to pendimethalin can occur by the oral route through food and other sources. Endothelial function is vital to numerous biological processes, and endothelial dysfunction and poor vascular health is associated with increased atherosclerotic events; however, no study has yet investigated the potential effect of pendimethalin on endothelial function and vasculature formation. The objective of the current study is to investigate if pendimethalin may affect the viability and function of vascular endothelial cells. We observed that pendimethalin significantly repressed viability of human endothelial cells, inducing G1 cell cycle arrest and apoptotic/necrotic cell death. Pendimethalin treatment also activated ER stress and autophagy, leading to loss of mitochondrial membrane potential. In addition, pendimethalin impaired the tube forming and migratory abilities of endothelial cells. This study provides previously unrecognized adverse effects of pendimethalin in vascular endothelial cells, mediated by ER stress-induced mitochondrial dysfunction.

Cannabidiol exerts anti-proliferative activity via a cannabinoid receptor 2-dependent mechanism in human colorectal cancer cells.

Colorectal cancer is the third leading cause of cancer incidence and mortality in the United States. Cannabidiol (CBD), the second most abundant phytocannabinoid in Cannabis sativa, has potential use in cancer treatment on the basis of many studies showing its anti-cancer activity in diverse types of cancer, including colon cancer. However, its mechanism of action is not yet fully understood. In the current study, we observed CBD to repress viability of different human colorectal cancer cells in a dose-dependent manner. CBD treatment led to G1-phase cell cycle arrest and an increased sub-G1 population (apoptotic cells); it also downregulated protein expression of cyclin D1, cyclin D3, cyclin-dependent kinase 2 (CDK2), CDK4, and CDK6. CBD further increased caspase 3/7 activity and cleaved poly(ADP-ribose) polymerase, and elevated expression of endoplasmic reticulum (ER) stress proteins including binding immunoglobulin protein (BiP), inositol-requiring enzyme 1α (IRE1α), phosphorylated eukaryotic initiation factor 2α (eIF2α), activating transcription factor 3 (ATF3), and ATF4. We found that CBD repressed cell viability and induced apoptotic cell death through a mechanism dependent on cannabinoid receptor type 2 (CB2), but not on CB1, transient receptor potential vanilloid, or peroxisome proliferator-activated receptor gamma. Anti-proliferative activity was also observed for other non-psychoactive cannabinoid derivatives including cannabidivarin (CBDV), cannabigerol (CBG), cannabicyclol (CBL), and cannabigerovarin (CBGV). Our data indicate that CBD and its derivatives could be promising agents for the prevention of human colorectal cancer.

Polyphenol Containing Sorghum Brans Exhibit an Anti-Cancer Effect in Apc Min/+ Mice Treated with Dextran Sodium Sulfate.

Colon cancer (CC) is considered a high-risk cancer in developed countries. Its etiology is correlated with a high consumption of red meat and low consumption of plant-based foods, including whole grains. Sorghum bran is rich in polyphenols. This study aimed to determine whether different high-phenolic sorghum brans suppress tumor formation in a genetic CC rodent model and elucidate mechanisms. Tissue culture experiments used colorectal cancer cell lines SW480, HCT-116 and Caco-2 and measured protein expression, and protein activity. The animal model used in this study was APC Min+/mouse model combined with dextram sodium sulfate. High phenolic sorghum bran extract treatment resulted in the inhibition of proliferation and induced apoptosis in CC cell lines. Treatment with high phenolic sorghum bran extracts repressed TNF-α-stimulated NF-κB transactivation and IGF-1-stimulated PI3K/AKT pathway via the downregulation of ß-catenin transactivation. Furthermore, high-phenolic sorghum bran extracts activated AMPK and autophagy. Feeding with high-phenolic sorghum bran for 6 weeks significantly suppressed tumor formation in an APC Min/+ dextran sodium sulfate promoted CC mouse model. Our data demonstrates the potential application of high-phenolic sorghum bran as a functional food for the prevention of CC.

Adverse effect of polystyrene microplastics (PS-MPs) on tube formation and viability of human umbilical vein endothelial cells.

Environmental contamination by microplastics (MPs) is an emerging concern in recent years due to associated adverse impacts of MPs on potential human health problems. Endothelial dysfunction is a condition in which the endothelial layer fails to form normally, and is associated with impaired vascular function. Despite the fact that MPs are known to enter the circulation system through intestinal epithelium, little has been known whether MPs impact the normal function of endothelial cells and the formation of vasculature. In the current study, we investigated the effect of polystyrene microplastics (PS-MPs) on tube formation and cytotoxicity in human umbilical vein endothelial cells (HUVECs). Our study showed that the treatment of HUVECs with PS-MPs significantly decreased cell viability, with intracellular accumulation occurring in a dose- and size-dependent manner. Moreover, significant dose-dependent inhibition of angiogenic tube formation was observed in HUVECs treated with 0.5 µm PS-MPs; this effect was accompanied by suppression of angiogenic signaling pathways and inhibitory activity against wound healing and cell migration. Regarding the mechanism of decreased viability, we observed increased autophagic and necrotic cell death. These results indicate that 6-h exposure of endothelial cells to PS-MPs represses tube-forming capacity, while 48-h exposure leads to autophagy and necrosis-mediated cytotoxicity.

A mechanistic review: potential chronic disease-preventive properties of sorghum.

Sorghum is one of the most widely cultivated crops, and is used in foods, domestic animal feedstuffs, alcohol production, and biofuels. Recently, many research groups have demonstrated that sorghum contains various components that are strongly associated with the prevention of major human chronic diseases such as obesity, diabetes, atherosclerosis, cancer, and inflammation. However, to use sorghum more widely as a food for the potential prevention and treatment of human chronic diseases, more studies will be required to elucidate the biological mechanisms. In this review paper, we highlight multiple findings to propose a mechanistic link between sorghum consumption and reduced risk of chronic diseases. © 2020 Society of Chemical Industry.