scholarly journals BZD9L1 sirtuin inhibitor as a potential adjuvant for sensitization of colorectal cancer cells to 5-fluorouracil

2019 ◽  
Vol 11 ◽  
pp. 175883591987897 ◽  
Author(s):  
Yi Jer Tan ◽  
Yeuan Ting Lee ◽  
Sven H. Petersen ◽  
Gurjeet Kaur ◽  
Koji Kono ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Combined Treatment ◽  
Single Treatment ◽  
Combined Treatments ◽  
Combination Treatments ◽  
Hct 116 ◽  
Hct 116 Cells ◽  
Tumour Proliferation

Background: This study aims to investigate the combination effect of a novel sirtuin inhibitor (BZD9L1) with 5-fluorouracil (5-FU) and to determine its molecular mechanism of action in colorectal cancer (CRC). Methods: BZD9L1 and 5-FU either as single treatment or in combination were tested against CRC cells to evaluate synergism in cytotoxicity, senescence and formation of micronucleus, cell cycle and apoptosis, as well as the regulation of related molecular players. The effects of combined treatments at different doses on stress and apoptosis, migration, invasion and cell death mechanism were evaluated through two-dimensional and three-dimensional cultures. In vivo studies include investigation on the combination effects of BZD9L1 and 5-FU on colorectal tumour xenograft growth and an evaluation of tumour proliferation and apoptosis using immunohistochemistry. Results: Combination treatments exerted synergistic reduction on cell viability on HCT 116 cells but not on HT-29 cells. Combined treatments reduced survival, induced cell cycle arrest, apoptosis, senescence and micronucleation in HCT 116 cells through modulation of multiple responsible molecular players and apoptosis pathways, with no effect in epithelial mesenchymal transition (EMT). Combination treatments regulated SIRT1 and SIRT2 protein expression levels differently and changed SIRT2 protein localization. Combined treatment reduced growth, migration, invasion and viability of HCT 116 spheroids through apoptosis, when compared with the single treatment. In addition, combined treatment was found to reduce tumour growth in vivo through reduction of tumour proliferation and necrosis compared with the vehicle control group. This highlights the potential therapeutic effects of BZD9L1 and 5-FU towards CRC. Conclusion: This study may pave the way for use of BZD9L1 as an adjuvant to 5-FU in improving the therapeutic efficacy for the treatment of colorectal cancer.

Anti-Colon Cancer Effects of 6-Shogaol Through G2/M Cell Cycle Arrest by p53/p21-cdc2/cdc25A Crosstalk

2015 ◽  
Vol 43 (04) ◽  
pp. 743-756 ◽  
Author(s):  
Lian-Wen Qi ◽  
Zhiyu Zhang ◽  
Chun-Feng Zhang ◽  
Samantha Anderson ◽  
Qun Liu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Colon Cancer ◽  
Cell Cycle Arrest ◽  
Strong Support ◽  
Cancer Chemoprevention ◽  
M Cell ◽  
Cycle Arrest ◽  
Hct 116 ◽  
Hct 116 Cells

Chemopreventive agents can be identified from botanicals. Recently, there has been strong support for the potential of 6-shogaol, a natural compound from dietary ginger (Zingiber officinale), in cancer chemoprevention. However, whether 6-shogaol inhibits the growth of colorectal tumors in vivo remains unknown, and the underlying anticancer mechanisms have not been well characterized. In this work, we observed that 6-shogaol (15 mg/kg) significantly inhibited colorectal tumor growth in a xenograft mouse model. We show that 6-shogaol inhibited HCT-116 and SW-480 cell proliferation with IC50 of 7.5 and 10 μM, respectively. Growth of HCT-116 cells was arrested at the G2/M phase of the cell cycle, primarily mediated by the up-regulation of p53, the CDK inhibitor p21waf1/cip1 and GADD45α, and by the down-regulation of cdc2 and cdc25A. Using p53-/- and p53+/+ HCT-116 cells, we confirmed that p53/p21 was the main pathway that contributed to the G2/M cell cycle arrest by 6-shogaol. 6-Shogaol induced apoptosis, mainly through the mitochondrial pathway, and the bcl-2 family might act as a key regulator. Our results demonstrated that 6-shogaol induces cancer cell death by inducing G2/M cell cycle arrest and apoptosis. 6-Shogaol could be an active natural product in colon cancer chemoprevention.

Atractylenolide III induces apoptosis by regulating the Bax/Bcl-2 signaling pathway in human colorectal cancer HCT-116 Cells in vitro and in vivo

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Dan Zhang ◽  
Xiaofang Xiao ◽  
Daqiang Song ◽  
Siwei Chen ◽  
Zhuo Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Signaling Pathway ◽  
Human Colorectal Cancer ◽  
Hct 116 ◽  
Hct 116 Cells ◽  
Atractylenolide Iii

scholarly journals Stabilization of UCA1 by N6-methyladenosine RNA methylation modification promotes colorectal cancer progression

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Rong-Zhang He ◽  
Jing Jiang ◽  
Xinglin Hu ◽  
Ming Lei ◽  
Jia Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Rna Methylation ◽  
Normal Tissues ◽  
Qrt Pcr ◽  
Hct 116 ◽  
Colorectal Cancer Progression ◽  
Hct 116 Cells ◽  
The Stability

Abstract Background UCA1 is frequently upregulated in a variety of cancers, including CRC, and it can play an oncogenic role by various mechanisms. However, how UCA1 is regulated in cancer is largely unknown. In this study, we aimed to determine whether RNA methylation at N6-methyladenosine (m6A) can impact UCA1 expression in colorectal cancer (CRC). Methods qRT-PCR was performed to detect the level of UCA1 and IGF2BP2 in CRC samples. CRISPR/Cas9 was employed to knockout (KO) UCA1, METTL3 and WTAP in DLD-1 and HCT-116 cells, while rescue experiments were carried out to re-express METTL3 and WTAP in KO cells. Immunoprecipitation using m6A antibody was performed to determine the m6A modification of UCA1. In vivo pulldown assays using S1m tagging combined with site-direct mutagenesis was carried out to confirm the recognition of m6A-modified UCA1 by IGF2BP2. Cell viability was measured by MTT and colony formation assays. The expression of UCA1 and IGF2BP2 in TCGA CRC database was obtained from GEPIA (http://gepia.cancer-pku.cn). Results Our results revealed that IGF2BP2 serves as a reader for m6A modified UCA1 and that adenosine at 1038 of UCA1 is critical to the recognition by IGF2BP2. Importantly, we showed that m6A writers, METTL3 and WTAP positively regulate UCA1 expression. Mechanically, IGF2BP2 increases the stability of m6A-modified UCA1. Clinically, IGF2BP2 is upregulated in CRC tissues compared with normal tissues. Conclusion These results suggest that m6A modification is an important factor contributing to upregulation of UCA1 in CRC tissues.

scholarly journals Genistein Inhibits Human Colorectal Cancer Growth and Suppresses MiR-95, Akt and SGK1

2015 ◽  
Vol 35 (5) ◽  
pp. 2069-2077 ◽  
Author(s):  
Jian Qin ◽  
Jia Xin Chen ◽  
Zhou Zhu ◽  
Jia An Teng
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Molecular Mechanisms ◽  
Xenograft Model ◽  
Inhibitory Effect ◽  
Protein Levels ◽  
Phosphorylated Akt ◽  
Hct 116 ◽  
Hct 116 Cells

Background: Genistein, a major isoflavonoid isolated from dietary soybean, has been shown to suppress the growth of several cancers through modulation of various pathways. However, the molecular mechanisms by which genistein elicit its effects on colorectal cancer (CRC) cells have not been fully elucidated. In this study, we aimed to investigate the anti-tumor activities of genistein on CRC and its potential mechanism. Methods: Effects of genistein on the cell proliferation were tested in HCT-116 cells by MTT assay, and apoptosis was measured by Flow cytometry. Real-time PCR was also used to evaluate the regulation of genistein on miR-95, Akt and SGK1 expression. The protein levels of total Akt (T-Akt), and phosphorylated Akt (P-Akt) were assessed by western blot. A nude mice xenograft model was employed to determine whether genistein could have an anti-tumor effect on CRC in vivo. Results: We found that treatment of HCT-116 cells with genistein caused an inhibition of cell proliferation and induction of apoptosis. Meanwhile, genistein down-regulated the mRNA expression of Akt, SGK1 and miR-95, and inhibited the phosphorylation of Akt in HCT-116 cells. The experiment in vivo also showed that genistein significantly suppressed the growth of mouse xenograft tumor. Conclusion: This study demonstrates that genistein has an inhibitory effect on CRC involved in reducing miR-95, Akt and SGK1, offering novel insights into the mechanisms of genistein therapeutic actions.

scholarly journals Inhibitory Effects of Peptide Lunasin in Colorectal Cancer HCT-116 Cells and Their Tumorsphere-Derived Subpopulation

2020 ◽  
Vol 21 (2) ◽  
pp. 537 ◽  
Author(s):  
Samuel Fernández-Tomé ◽  
Fei Xu ◽  
Yanhui Han ◽  
Blanca Hernández-Ledesma ◽  
Hang Xiao
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Kinase Inhibitor ◽  
G1 Phase ◽  
Inhibitory Effects ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Hct 116 ◽  
Hct 116 Cells ◽  
Induced Apoptosis ◽  
Chemopreventive Activity

The involvement of cancer stem-like cells (CSC) in the tumor pathogenesis has profound implications for cancer therapy and chemoprevention. Lunasin is a bioactive peptide from soybean and other vegetal sources with proven protective activities against cancer and other chronic diseases. The present study focused on the cytotoxic effect of peptide lunasin in colorectal cancer HCT-116 cells, both the bulk tumor and the CSC subpopulations. Lunasin inhibited the proliferation and the tumorsphere-forming capacity of HCT-116 cells. Flow cytometry results demonstrated that the inhibitory effects were related to apoptosis induction and cell cycle-arrest at G1 phase. Moreover, lunasin caused an increase in the sub-GO/G1 phase of bulk tumor cells, linked to the apoptotic events found. Immunoblotting analysis further showed that lunasin induced apoptosis through activation of caspase-3 and cleavage of PARP, and could modulate cell cycle progress through the cyclin-dependent kinase inhibitor p21. Together, these results provide new evidence on the chemopreventive activity of peptide lunasin on colorectal cancer by modulating both the parental and the tumorsphere-derived subsets of HCT-116 cells.

scholarly journals Effects of Curcumin in Combination with Doxorubicin in Human Colorectal Cancer Cell Line

2019 ◽  
Vol 3 (4) ◽  
pp. 89-92
Author(s):  
Zakieh Rostamzadeh Khameneh ◽  
Mahshid Mohammadian ◽  
Mohammad Aziz Rasouli ◽  
Zhino Moradi ◽  
Zohre Ahmadi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Wide Spectrum ◽  
Cancer Cell Line ◽  
Cost Effective ◽  
Water Soluble ◽  
Colorectal Cancer Cell Line ◽  
Main Role ◽  
Combination Treatments ◽  
Hct 116 ◽  
Hct 116 Cells

Background: Colorectal cancer (CRC) is one of the main cause of cancer related death worldwide. New therapeutic strategies are required for CRC. Anthracycline drugs such as doxorubicin (DOX) remain one of the most active wide-spectrum and cost-effective drugs in cancer therapy. However, colorectal cancer (CRC) cells are inherently resistant to anthracyclines. Curcumin, the active component and yellow pigment, has been considered as anti-cancer agents with anti-proliferation, anti-invasion, and anti-angiogenesis properties. Previous data show that curcumin may played main role as therapeutic agent for CRC. We aimed to assess the possible sensitizing effects of curcumin in HCT-116 CRC cells treated with DOX.Methods: HCT-116 cells were treated with different doses of curcumin and DOX in increasing concentrations and cytotoxicity were evaluated after 48 h by Water Soluble Tetrazolium Salts(WST-1) method. In double combination treatments (48 h), the mentioned concentration were utilized; D ( Curcumin; 20 μM;DOX;5μM) C (Curcumin; 10 μM;DOX ;2.5μM ), B (Curcumin; 5 μM;DOX;1μM) and A (Curcumin; 2.5 μM;DOX;0.5μM).Results: HCT-116 cells treatments with various concentrations of single agents (DOX and curcumin) decreased the cellular viability in a dose-dependent pattern. Here, we show that treatment of HCT-116 CRC cells with curcumin increases the efficacy of DOX-induced death in HCT-116 cells. Curcumin treatments also results in higher cytotoxicity of DOX and the cell death percent in compared to higher doses in single treatments.Conclusion: It could be concluded that curcumin could acts as chemosensitiser towards the DOX therapy. So it might be used as adjuvant therapy to enhance DOX sensitivity in CRC cells.

scholarly journals Natural Hypoxia is Not a Limiting Factor in Evaluating the Novel Arylidene Derivative MLT-401 Against an In Vitro Colorectal Cancer Model

2018 ◽  
Vol 46 (5) ◽  
pp. 2082-2089 ◽  
Author(s):  
Ismaeel  Bin-Jaliah
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Apoptotic Cell ◽  
Limiting Factor ◽  
Cancer Model ◽  
Hypoxic Conditions ◽  
Hct 116 ◽  
Hct 116 Cells

Background/Aims: Cancer cells in vivo develop resistance to many anti-tumor drugs. One known factor to influence such drug resistance is hypoxia, which is an important component of the tumor microenvironment. Standard cancer lines mostly do not exhibit a cellular hypoxic microenvironment and there is a paucity of information on the efficacy of lead molecules in both cellular- and environment-induced hypoxic conditions. Therefore, in the present study, we have evaluated the efficacy of the arylidene derivative MLT-401, a lead molecule showing activity against colorectal cancer model using the HCT 116 cell line and CCD-80-C control cells in normoxic and natural (marginal) hypoxic conditions, which is usually observed in high-altitude regions. Methods: The efficacy of MLT-401 on HCT 116 and CCD-80-C cells were tested in both normoxia and marginal hypoxia conditions. MTT assay was used to evaluate cell proliferation, Annexin V binding assay for apoptotic cell quantification and PI staining for cell cycle were done by flow cytometry. Induction of pro-apoptotic marker BAX and anti-apoptotic Bcl-2 were assessed by western blot. Bcl-2/BAX ratio was calculated based on protein expression by western blotting and bands were quantified by Image J software. Results: Analysis of cell proliferation showed an average 10-fold reduction in the inhibition of HCT 116 cells in hypoxic conditions with approximately 500 nM MLT-401, while there was no significant change noted in marginal hypoxic conditions. A proportionate increase in the number of apoptotic cells and large M4 fraction of 10.5% and 26.7% of HCT116 against 6.3% of control cells in cell cycle assessment with MLT-401 concentrations ranging from 250 to 500 nM respectively clearly demonstrated anti-cancer activity. A Bcl-2/BAX ratio of < 1 showed that the induction of apoptosis was the gross mechanism underlying the inhibition of HCT 116 cells by MLT-401. Conclusion: Collectively, these results show MLT-401 as an effective anti-colorectal cancer lead molecule irrespective of normoxia or natural hypoxia.

scholarly journals Mesenchymal Stem Cell-derived Extracellular Vesicles Transmitting MicroRNA-34a-5p Suppress Tumorigenesis of Colorectal Cancer Through c-MYC/DNMT3a/PTEN Axis

2021 ◽  
Author(s):  
Jiangning Zhao ◽  
Huanrong Lin ◽  
Kunsong Huang
Keyword(s):  
Colorectal Cancer ◽  
Stem Cell ◽  
Cell Growth ◽  
Mesenchymal Stem Cell ◽  
Extracellular Vesicles ◽  
Dna Methyltransferase ◽  
Tumor Formation ◽  
Hct 116 ◽  
Hct 116 Cells

AbstractMesenchymal stem cell–derived extracellular vesicles (MSC-EV) can transport microRNAs (miRNAs) into colorectal cancer (CRC) cells, thus to inhibit the malignant phenotype of cancer cells. Whether MSC-EV could deliver miR-34a-5p to suppress CRC development was surveyed through the research. miR-34a-5p, c-MYC, DNA methyltransferase 3a (DNMT3a), and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expression were measured in CRC tissues and cell lines. miR-34a-5p and c-MYC expression were altered by transfection in HCT-116 cells. MSC-EV were transfected with miR-34a-5p- and c-MYC-related oligonucleotides and co-cultured with HCT-116 cells. HCT-116 cell growth after treatment was observed. Furthermore, the functional roles of miR-34a-5p and c-MYC were explored in vivo. The combined interactions of miR-34a-5p/c-MYC/DNMT3a/PTEN axis were assessed. miR-34a-5p and PTEN were downregulated while c-MYC and DNMT3a were upregulated in CRC. Depletion of miR-34a-5p drove while that of c-MYC restricted CRC cell growth. MSC-EV retarded CRC progression. Moreover, MSC-EV carrying overexpressed miR-34a-5p or depleted c-MYC further disrupted CRC cell progression. miR-34a-5p targeted c-MYC to regulate DNMT3a and PTEN. c-MYC overexpression abrogated EV-derived miR-34a-5p upregulation-induced effects on CRC. Restoring miR-34a-5p or depleting c-MYC in MSC-EV limited CRC tumor formation. MSC-EV-derived miR-34a-5p depresses CRC development through modulating the binding of c-MYC to DNMT3a and epigenetically regulating PTEN.

scholarly journals Impact of temperature and radiation on elimination of associated bacteria from preserved dried prawn, Macrobrachium lamerrei

2016 ◽  
Vol 3 (1) ◽  
pp. 1-7
Author(s):  
Md Enamul Haque ◽  
Tahmina Afroz ◽  
H Rashid
Keyword(s):  
Combined Treatment ◽  
Total Coliform ◽  
Treatment Temperature ◽  
Single Treatment ◽  
Combined Treatments ◽  
Bacterial Strains ◽  
Associated Bacteria ◽  
Combination Treatments ◽  
Different Temperatures ◽  
The Impact

The impact of different temperatures (0, 40, 60, 80 and 100° C for an hour) and radiation (0, 2.5, 5.0, 7.5 and 10.0 kGy) and combined treatment (temperature and radiation) for decontamination of bacteria from dried prawn, Macrobrachium lamarrei was also investigated under laboratory condition.The total viable bacterial (TVB), total staphylococcal (TS), total coliform (TC), total faecal coliform (TFC), total Aeromonas ( TA) and total fungal (TF) count were ranged from 2.7×108 to 5.3×108 cfu/g, 2.2×106 to 6.0×106 cfu/g, 2.9×104 to 9.5×104 cfu/g, 2.8×103 to 8.1×103 cfu/g, 5.7×103 to 8.5×103 cfu/g and 1.6×104 to 3.8×104 cfu/g respectively. Seventy eight bacterial strains were isolated and identified out of which 18 (23.07 %) were Staphylococcus aureus, 11 (14.10% ) were Micrococcus varians, 8 (10.25%) were Aeromonas hydrophila, 5 (6.41%) were Klebsiella ozaenae, 7 (8.97%) were Bacillus subtilis, 7 (8.97%) were Escherichia coli, 5 (6.41%) were Bacillus megaterium, 7 (8.97%) were Klebsiella edwardsii, 6 (7.69%) were Pseudomonas aeruginosa and 4 (5.12%) were Micrococcus radiodurans. Inactivated was more favorable at 100° C for TC, TFC, TA and TF and at 5.0 kGy for TA and TF and combined treatments (40° C+2.5 kGy, 60° C+2.5 kGy and 80° C+2.5 kGy) for TFC, TA and TF respectively. TS, TC and TVB were completely eliminated in treatment 40° C+5.0 kGy, 60° C+2.5 kGy, 80° C+2.5 kGy, 40° C+7.5 kGy, 60° C+7.5 kGy and 80° C+7.5 kGy respectively. Results demonstrated that the combination treatments were more effective than single treatment for eliminating the associated microorganisms/bacteria from dried prawn.Jahangirnagar University J. Biol. Sci. 3(1): 1-7, 2014 (June)

scholarly journals miR-20b-5p Functions as Tumor Suppressor microRNA by targeting CyclinD1 in Colon Cancer

2020 ◽  
Author(s):  
Hui Yang ◽  
Jian Lin ◽  
Jinling Jiang ◽  
Jun Ji ◽  
Chao Wang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Colon Cancer ◽  
Tumor Suppressor ◽  
Migration And Invasion ◽  
Migration Assay ◽  
Subcutaneous Xenograft ◽  
Hct 116 ◽  
Xenograft Models ◽  
Hct 116 Cells

Abstract Background MicroRNA functions as an oncogenic regulator or tumor suppressor in various human tumors. Bioinformatics analysis revealed that miRNA-20b is related to the tumorigenesis, however, the function of miRNA-20b in colon cancer is still not clear. Methods Apoptosis, cell cycle, expression of CCND1/CDK/FOXM1 axis in HCT116 cells were examined by flow cytometry, western blot, and Immunohistochemistry. Wound-healing migration assay and transwell assay were performed to test the migration and invasion of tumor cells. Bioinformatics and microarray analysis was performed for further mechanical research. Subcutaneous xenograft mouse models was to verify the function of miR-20b-5p in vivo. Results We found that miRNA-20b-5p inhibited the cell cycle, migration and invasion of CC cells, but had no effect on cell apoptosis. CyclinD1(CCND1) was identified as a direct target of miR-20b-5p. Overexpression of miRNA-20b-5p downregulated CCND1 level in HCT-116 cells. Mechanistically, the inhibiton of cell cycle, migration and invasion of CC cells by miRNA-20b-5p is through regulating the CCND1/CDK4/FOXM1 axis. Additionally, we found that miRNA-20b-5p could inhibit the tumorigenesis in murine CC xenograft models in Balb/c nude mice. Conclusion Therefore, our findings demonstrated that miR-20b-5p may serve as a tumor suppressor in CC by negatively regulating CCND1 and that miR-20b-5p may be a potential therapeutic target for the management and treatment of colon cancer.

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