Low Molecular Weight Procyanidins from Grape Seeds Enhance the Impact of 5-Fluorouracil Chemotherapy on Caco-2 Human Colon Cancer Cells

Abstract Objectives Plant secondary metabolites, such as polyphenols, are found in many fruits, grains, and vegetables, and are thus a part of normal human diet. One such food is sorghum (Sorghum bicolor), a cereal grain that contains varying concentrations of polyphenols. Many polyphenols have been implicated in the regulation of colon cancer through modulating the antioxidant defense, which includes some of the major selenoproteins, e.g., thioredoxin reductases (TXNRD) and glutathione peroxidases (GPX). However, because such redox-active enzymes have been shown to be involved in both cancer prevention and promotion, the goal of our study is to assess the impact of high-polyphenol sorghum extracts on the expression of selenoproteins. Methods Human colon cancer cells (HT29, HCT116) were incubated with 1.25 mg high-polyphenol sorghum bran extract per mL medium for 48 h. RNA was extracted with Trizol/Chloroform, and reverse-transcribed to cDNA. mRNA expression of selenoproteins was quantitated using qPCR, normalized to GAPDH, and analyzed using GraphPad Prism. Protein lysates will be used for Western blotting and catalytic activity assays. Results Compared to solvent control, incubation of human colon cancer cells with high-polyphenol sorghum extracts for 48 h moderately impacted mRNA expression of investigated selenoproteins. One of the extracts resulted in a nearly doubled GPX1 mRNA expression in HCT116 cells (p = 0.08), whereas preliminary results suggest that TXNRD1 expression may be lowered. Conclusions High-polyphenol varieties of sorghum may affect selenoprotein expression. Further investigations involving both shorter and longer-term incubation times, as well as effects on protein expression and activity will help elucidate the effects of these new sorghum varieties on selenoprotein expression important in prevention and promotion of colon cancer. Funding Sources Financial support was provided by Towson University's Fisher College of Science and Mathematics (P. Tsuji) and the USDA (D. Smolensky).

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Antitumor potential of new low molecular weight antioxidative preparations from the white rot fungus Cerrena unicolor against human colon cancer cells

Scientific Reports ◽

10.1038/s41598-018-37947-z ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 10

Author(s):

Anna Matuszewska ◽

Dawid Stefaniuk ◽

Magdalena Jaszek ◽

Mateusz Pięt ◽

Adrian Zając ◽

...

Keyword(s):

Molecular Weight ◽

Colon Cancer ◽

Human Colon ◽

White Rot ◽

White Rot Fungus ◽

Low Molecular Weight ◽

Colon Cancer Cells ◽

Human Colon Cancer ◽

Antitumor Potential ◽

Human Colon Cancer Cells

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Impact of Sorghum Polyphenols on Expression of Carcinogen-Metabolizing Enzymes in Human Colon Cancer Cells (P06-046-19)

Current Developments in Nutrition ◽

10.1093/cdn/nzz031.p06-046-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Author(s):

Heather Buck ◽

Dmitriy Smolensky ◽

Petra Tsuji

Keyword(s):

Colon Cancer ◽

Mrna Expression ◽

Cancer Cells ◽

Human Colon ◽

Colon Cancer Cells ◽

Human Colon Cancer ◽

Metabolizing Enzymes ◽

Cereal Grain ◽

The Impact ◽

Human Colon Cancer Cells

Abstract Objectives Polyphenols are plant secondary metabolites found in many fruits, grains, and vegetables, and are thus a part of normal human diet. One such food is sorghum (Sorghum bicolor), a cereal grain that contains varying concentrations of polyphenols. Many polyphenols have been implicated in the regulation of bioactivating (phase 1) and bioinactivating (phase 2) enzymes. The goal of this study is to assess the impact of sorghum polyphenol extracts on the expression of xenobiotic-activating and -inactivating enzymes important in cancer prevention and promotion. Methods Polyphenols were extracted from two types of sorghum bran. Human colon cancer cells (HT29, HCT116) were incubated with 1.25 mg extract per mL medium for 48 hours. RNA was extracted with Trizol/Chloroform, and reverse-transcribed to cDNA. mRNA expression of carcinogen-activating and -inactivating enzymes are quantitated using qPCR, normalized to GAPDH as internal control, and analyzed using GraphPad Prism. Protein extracts will be used for Western blotting to assess impact on protein expression and enzymatic activity. Results Compared to solvent control, mRNA expression of the arylhydrocarbon receptor (AHR) nuclear transferase (ARNT) increased in HT29 cells exposed to a novel high-polyphenol abstract (N = 4, p = 0.0017), whereas expression of AHR itself remained unaffected. Preliminary data suggest that expression of carcinogen-metabolizing enzymes, such as CYP1A1, may also increase in colon cancer cells upon exposure to the novel high-polyphenol extract. Conclusions The balance of xenobiotic-bioactivating and –inactivating enzymes is important to consider, as we investigate carcinogenesis and its prevention using dietary micronutrients. We continue to elucidate the expression and activity of such phase I and II enzymes in colon cancer cell models exposed to polyphenolic extracts. Funding Sources Financial support was provided by Towson University's Fisher College of Science and Mathematics (P. Tsuji), and the USDA (D. Smolensky).

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