Effect of indomethacin on the growth response, c-myc mRNA expression, and hTERT mRNA expression in colon cancer cells

2001 ◽  
Vol 120 (5) ◽  
pp. A165-A165
Author(s):  
T SHIMADA ◽  
T KUNIYOSHI ◽  
K KOJIMA ◽  
Y MITOBE ◽  
T MITSUHASHI ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Mrna Expression ◽  
Cancer Cells ◽  
Growth Response ◽  
Htert Mrna ◽  
Colon Cancer Cells ◽  
Htert Mrna Expression

Effect of indomethacin on the growth response, c-myc mRNA expression, and hTERT mRNA expression in colon cancer cells

2001 ◽  
Vol 120 (5) ◽  
pp. A165
Author(s):  
Tadahito Shimada ◽  
Toru Kuniyoshi ◽  
Kazuo Kojima ◽  
Yasuo Mitobe ◽  
Takahiro Mitsuhashi ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Mrna Expression ◽  
Cancer Cells ◽  
Growth Response ◽  
Htert Mrna ◽  
Colon Cancer Cells ◽  
Htert Mrna Expression

scholarly journals Uremic serum residue decreases SN-38 sensitivity through suppression of organic anion transporter polypeptide 2B1 in LS-180 colon cancer cells

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Shoichi Ozawa ◽  
Masayuki Tsujimoto ◽  
Hitoshi Uchiyama ◽  
Natsuko Ito ◽  
Satoe Morishita ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Mrna Expression ◽  
Cancer Cells ◽  
Organic Anion ◽  
Human Colon ◽  
Organic Anion Transporter ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Anion Transporter ◽  
Uremic Serum

Abstract Pharmacokinetics of SN-38 in patients with end-stage kidney disease (ESKD) is partially varied because of fluctuations in transporters expression and/or function by high protein bound-uremic toxins concentration. The fluctuations may induce variations in anticancer drugs sensitivity to cancer cells. We aimed to clarify the variations in sensitivity of SN-38 to cancer patients with ESKD and investigate this mechanism, by human colon cancer cells exposed to uremic serum residue. LS180 cells were exposed to normal or uremic serum residue (LS/NSR or LS/USR cells) for a month. IC50 values of SN-38 in LS/NSR or LS/USR cells were calculated from viability of each cells treated SN-38. mRNA expression and intracellular SN-38 accumulation was evaluated by RT-PCR and HPLC-fluorescence methods, respectively. The IC50 value in LS/USR cells was higher than that in LS/NSR cells. Organic anion transporter polypeptide (OATP) 2B1 mRNA expression was lower in LS/USR cells than in LS/NSR cells, and SN-38 accumulation in LS/USR cells was lower than that in LS/NSR cells. Only co-treatment baicalin, which is OATP2B1 inhibitor, almost negated the difference in SN-38 accumulation between LS/NSR and LS/USR. Anticancer effects of substrates of OATP2B1, such as SN-38, were reduced in ESKD patients at the same plasma substrate concentration.

scholarly journals Impact of High-Polyphenol Sorghum Varieties on Expression of Selenoproteins in Human Colon Cancer Cells (P06-047-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Ashish Singh ◽  
Dmitriy Smolensky ◽  
Petra Tsuji
Keyword(s):  
Colon Cancer ◽  
Mrna Expression ◽  
Cancer Cells ◽  
Plant Secondary Metabolites ◽  
Human Colon ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Cereal Grain ◽  
The Impact ◽  
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).

scholarly journals Impact of Sorghum Polyphenols on Expression of Carcinogen-Metabolizing Enzymes in Human Colon Cancer Cells (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).

scholarly journals The Effect of Sorghum Polyphenols on DNA Methylation and Histone Acetylation in Colon Cancer

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 328-328
Author(s):  
Zeguela Kamagate ◽  
Ashish Singh ◽  
Dmitriy Smolensky ◽  
Petra Tsuji
Keyword(s):  
Colorectal Cancer ◽  
Dna Methylation ◽  
Colon Cancer ◽  
Protein Expression ◽  
Histone Acetylation ◽  
Mrna Expression ◽  
Cancer Cells ◽  
Public Health Issue ◽  
Epigenetic Mechanisms ◽  
Colon Cancer Cells

Abstract Objectives Colorectal cancer (CRC) is a major public health issue, accounting for nearly 150,000 cases annually. Because CRC correlates with oxidative stress, exploiting the antioxidative nature of bioactive components in our diet that could potentially inhibit cancer promotion might be beneficial. New varietals of the grain Sorghum bicolor contain high amounts of polyphenols, which may contribute to CRC prevention due to their strong antioxidative and anti-carcinogenic properties. Because gene expression of enzymes may be mediated by epigenetic mechanisms, we are interested in DNA methylation and histone acetylation patterns of genes, including those enzymes that play a role in the promotion or prevention of CRC. Our objective is to examine how high-polyphenol sorghum varietals impact epigenetic mechanisms in human colon cancer cells. Methods We are currently assessing mRNA and protein expression, catalytic activity of DNA-methyltransferases (DNMTs) and histone acetyltransferases, in addition to global DNA methylation and histone acetylation in human HCT116 and CACO-2 colon cancer cells. We treated HCT116 cells with new high-polyphenol or commercially available S. bicolor extracts, solvent control, or 5 μM epigallocatechin gallate as a positive control for up to 48 hours. Total RNA, protein, and DNA were harvested, and mRNA expression of selected genes was quantitated with qPCR, and protein expression is being quantitated with Western blotting. Results Our preliminary results suggest that high-polyphenol S. bicolor may decrease mRNA expression of DNMT1, the key enzyme that upholds methylation patterns after DNA synthesis. Furthermore, mRNA expression of DNMT3A, the enzyme responsible for de novo DNA methylation, was also decreased. We will further investigate global and gene-specific DNA methylation, and the expression of genes involved in tumorigenesis and chemoprevention. Conclusions Consumption of high-polyphenol S. bicolor as part of the human diet may lead to beneficial changes in chromatin methylation or acetylation. Subsequently, the expression of specific genes involved in the promotion or prevention of colorectal cancer may be modified, providing a dietary intervention to CRC. Funding Sources Towson University. Bridges-to-Doctorate grant. USDA ARS Kansas.

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