Methylation of the ESR1 CpG island in the colorectal mucosa is an ‘all or nothing’ process in healthy human colon, and is accelerated by dietary folate supplementation in the mouse

2005 ◽  
Vol 33 (4) ◽  
pp. 709-711 ◽  
Author(s):  
N.J. Belshaw ◽  
G.O. Elliott ◽  
E.A. Williams ◽  
J.C. Mathers ◽  
L. Buckley ◽  
...  

ESR1 is frequently silenced by CGI (CpG island) methylation, both in human colorectal tumours and, in an age-dependent manner, in healthy mucosa. It is not clear, however, whether methylation of individual cytosines occurs randomly within the epithelial genome, or preferentially within individual cells as an ‘all-or-nothing’ phenomenon. CGI methylation can be quantified in human DNA residues recovered from faecal samples. We used bisulphite genomic sequencing of human DNA from this source and from a colorectal cancer cell line (SW48) to show that the ESR1 CGI is methylated in an allele-specific manner. This provides support for the ‘all or none’ mechanism for methylation of this gene, and shows how age-dependent methylation of the ESR1 CGI leads rapidly to silencing of the gene within the cells, and hence the colonic crypt within which it occurs. Preliminary studies with a rodent model suggest the rate of age-dependent methylation of ESR1 is modifiable by dietary folate.

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3937
Author(s):  
Hae-Jung Chae ◽  
Geum-Jin Kim ◽  
Barsha Deshar ◽  
Hyun-Jin Kim ◽  
Min-Ji Shin ◽  
...  

Colorectal cancer is one of the life-threatening ailments causing high mortality and morbidity worldwide. Despite the innovation in medical genetics, the prognosis for metastatic colorectal cancer in patients remains unsatisfactory. Recently, lichens have attracted the attention of researchers in the search for targets to fight against cancer. Lichens are considered mines of thousands of metabolites. Researchers have reported that lichen-derived metabolites demonstrated biological effects, such as anticancer, antiviral, anti-inflammatory, antibacterial, analgesic, antipyretic, antiproliferative, and cytotoxic, on various cell lines. However, the exploration of the biological activities of lichens’ metabolites is limited. Thus, the main objective of our study was to evaluate the anticancer effect of secondary metabolites isolated from lichen (Usnea barbata 2017-KL-10) on the human colorectal cancer cell line HCT116. In this study, 2OCAA exhibited concentration-dependent anticancer activities by suppressing antiapoptotic genes, such as MCL-1, and inducing apoptotic genes, such as BAX, TP53, and CDKN1A(p21). Moreover, 2OCAA inhibited the migration and invasion of colorectal cancer cells in a concentration-dependent manner. Taken together, these data suggest that 2OCAA is a better therapeutic candidate for colorectal cancer.


2020 ◽  
Author(s):  
Elham Taheri ◽  
Saba Ghorbani ◽  
Maryam Safi ◽  
Nasrin Seyyed Sani ◽  
Fatemeh Firouzi Amoodizaj ◽  
...  

Treatment of colorectal cancer is one of the important challenges due to the increase of resistance to chemotherapeutic drugs. Isolated natural compounds from medicinal plants and other sources often are used as novel drugs for treatment of various human cancer. The aim of this study was to investigate the antioxidant and anticancer activity of Eucalyptus camaldulensis essential oil on colorectal cancer cell line Caco-2. The antioxidant activity of extracted E. camaldulensis essential oil (1000, 800, 400, 200, 100, 50, 25, 12.5, 6, and 3 μg/mL) was evaluated by free radicals inactivation method. Moreover, MTT assay was used to examine the cytotoxic effects of E. camaldulensis essential oil on the Caco-2 cell line. The mRNA expression of BAX and BCL-2 genes was studied using quantitative Real-Time PCR method, in treated cancer cells compared to untreated cells. We indicated a significant, impressive antioxidant activity in 1000 μg/mL of E. camaldulensis essential oil, in a concentration-dependent manner. In addition, we found that this product exerted a cytotoxic effect on cancer cells when 100 μg/mL concentration was considered as half-maximal inhibitory concentration (IC50). Also, the expression of BAX and BCL-2 genes were significantly upregulated and downregulated, respectively, in the treated Caco-2 cells with E. camaldulensis essential oil. In conclusion, our study showed significant antioxidant and anticancer activity in E. camaldulensis essential oil in a concentration and time-dependent manner, which may be due to the reduction of free radicals and induction of apoptosis process in colorectal cancer cells.


2021 ◽  
Vol 26 (6) ◽  
pp. 3120-3128
Author(s):  
M. AYDIN AKBUDAK ◽  
TEVHIDE SUT ◽  
NURANIYE ERUYGUR ◽  
ERSIN AKINCI

The Epilobium species, rich in various active phytochemicals, have been widely used in folk medicine to treat several diseases including benign prostatic hyperplasia. Despite being demonstrated on some type of cancer cells such as prostate cancer, their potential anti-cancerous role on colorectal adenocarcinoma cells has not been studied yet. According to the World Health Organization (WHO), colon cancer is the third most common form of cancer, resulting over 800 000 deaths every year worldwide. The present study demonstrates the anti-cancerous activity of aqueous and ethanolic Epilobium parviflorum extracts in colon cancer cell line HT-29 cells in vitro. The both type of extracts reduced the cell viability of HT-29 cells in a dose dependent manner. Gene expression analysis of HT-29 cells demonstrated an increase at apoptotic genes, caspase 3 and caspase 8. Nuclear fragmentation of apoptotic cells was also demonstrated through TUNEL assay as well as immunostaining experiments. On the other hand, same lethal concentrations of E. parviflorum extracts were not profound on non-cancerous human fibroblast cell line BJ cells. Our results indicate that E. parviflorum may also be used as a therapeutic agent against colon cancers.


2020 ◽  
Vol 44 (1) ◽  
pp. 68-74
Author(s):  
Hussein A. Khayoon

This study aimed to examine the cytotoxic effect of resveratrol as an anticancer in human colorectal cancer (HRT) cell line by assessment of its half-maximal inhibitory concentration (IC50) and its ability to inhibit the growth of these cancerous cells. Resveratrol inhibited the proliferation of HRT cell lines when used at different increased concentrations in this study (25, 50, 100, 200, 300) μmol respectively. These increased concentrations of resveratrol caused a corresponding significant inhibition in the growth percentage of the tested cancerous cell line (13%, 31.33%, 53.66%, 63.66 %, and 76.33%) respectively when compared with DMSO0.1% as negative control, in a concentration-dependent manner. Resveratrol at 300 μmol concentration showed the highest significant increase in the growth inhibitory percentage (76.33%). Moreover, resveratrol IC50 against (HRT) cell line was determined as 75.63 μmol. The study suggested a promising anticancer activity of resveratrol which can interfere with many dysregulated signaling pathways in transformed cells which are proposed to be driving forces for its anticancer effect.


2020 ◽  
Author(s):  
M. AYDIN AKBUDAK ◽  
Tevhide SUT ◽  
Nuraniye ERUYGUR ◽  
Ersin AKINCI

The Epilobium species are rich in various active phytochemicals and have seen wide use in folk medicine to treat several diseases, including benign prostatic hyperplasia. Although their benefits have been demonstrated on certain types of cancer cells, such as prostate cancer cells, their potential antiproliferative effects on colorectal adenocarcinoma cells have yet to be studied. The present study exhibited the antiproliferative activity of aqueous and ethanolic Epilobium parviflorum extracts in a colon cancer cell line, HT-29 cells in vitro. Both types of extracts reduced the cell viability of HT-29 cells in a dose-dependent manner. A gene expression analysis of the HT-29 cells demonstrated an increase in apoptotic genes, Caspase-3 and Caspase-8. Nuclear fragmentation of the apoptotic cells was also demonstrated through TUNEL assay and immunostaining experiments. On the other hand, the same lethal concentrations of the E. parviflorum extracts did not significantly affect a non-cancerous human fibroblast cell line, BJ cells. Our results confirmed that aqueous and ethanolic Epilobium parviflorum extracts can eliminate proliferation of human colorectal carcinoma cells in vitro. E. parviflorum may have the potential to become a therapeutic agent against colon cancers.


Author(s):  
Merve Erkisa ◽  
Nazlihan Aztopal ◽  
Elif Erturk ◽  
Engin Ulukaya ◽  
Veysel T. Yilmaz ◽  
...  

Background: Cancer stem cells (CSC) are subpopulation within the tumor that acts a part in the initiation, progression, recurrence, resistance to drugs and metastasis of cancer. It is well known that epigenetic changes lead to tumor formation in cancer stem cells and show drug resistance. Epigenetic modulators and /or their combination with different agents have been used in cancer therapy. Objective: In our study we scope out the effects of combination of a histone deacetylases inhibitor, valproic acid (VPA), and Cu(II) complex [Cu(barb-κN)(barb-κ2N,O)(phen-κN,N’)]·H2O] on cytotoxicity/apoptosis in a stem-cell enriched population (MCF-7s) obtained from parental breast cancer cell line (MCF-7). Methods: Viability of the cells was measured by the ATP assay. Apoptosis was elucidated via the assessment of caspase-cleaved cytokeratin 18 (M30 ELISA) and a group of flow cytometry analysis (caspase 3/7 activity, phosphatidylserine translocation by annexin V-FITC assay, DNA damage and oxidative stress) and 2ˈ,7ˈ–dichlorofluorescein diacetate staining. Results: The VPA combined with Cu(II) complex showed anti proliferative activity on MCF-7s cells in a dose- and time-dependently. Treatment with combination of 2.5 mM VPA and 3.12 μM Cu(II) complex induces oxidative stress in a time-dependent manner, as well as apoptosis that is evidenced by the increase in caspase 3/7 activity, positive annexin-V-FITC, and increase in M30 levels. Conclusion: The results suggest that the combination therapy induces apoptosis following increased oxidative stress, thereby making it a possible promising therapeutic strategy that further analysis is required.


2018 ◽  
Vol 18 (4) ◽  
pp. 573-582 ◽  
Author(s):  
Khaled R.A. Abdellatif ◽  
Mostafa M. Elbadawi ◽  
Mohammed T. Elsaady ◽  
Amer A. Abd El-Hafeez ◽  
Takashi Fujimura ◽  
...  

Background: Some 2-thioxoimidazolidinones have been reported as anti-prostate and anti-breast cancer agents through their inhibitory activity on topoisomerase I that is considered as a potential chemotherapeutic target. Objective: A new series of 3,5-disubstituted-2-thioxoimidazolidinone derivatives 10a-f and their S-methyl analogs 11a-f were designed, synthesized and evaluated for cytotoxicity against human prostate cancer cell line (PC-3), human breast cancer cell line (MCF-7) and non-cancerous human lung fibroblast cell line (WI-38). </P><P> Results and Method: While compounds 10a-f showed a broad range of activities against PC-3 and MCF-7 cell lines (IC50 = 34.0 – 186.9 and 24.6 – 147.5 µM respectively), the S-methyl analogs 11a-f showed (IC50 = 22.7 – 198.5 and 16.9 – 188.2 µM respectively) in comparison with 5-fluorouracil (IC50 = 60.7 and 40.7 µM respectively). 11c (IC50 = 22.7 and 29.2 µM) and 11f (IC50 = 28.7 and 16.9 µM) were the most potent among all compounds against both PC-3 and MCF-7 respectively with no cytotoxicity against WI-38. Conclusion: The newly synthesized compounds showed good activity against PC-3 and MCF-7 cell lines in comparison with 5-fluorouracil. Compounds 11c and 11f bound with human topoisomerase I similar to its known inhibitors and significantly inhibited its DNA relaxation activity in a dose dependent manner which may rationalize their molecular mechanism as cytotoxic agents.


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