Sodium butyrate induces apoptosis and regulates caspase-3 in colorectal cancer cells COLO205

Background: Anlotinib is a multi-target tyrosine kinase inhibitor that has been reported to have activity against colorectal cancer. However, the mechanisms of how anlotinib mediates drug-resistance of colorectal cancer have not been fully described. Particularly the potential mechanisms regarding to the inhibition of proliferation and induction of apoptosis remain unknown. Objective: In this study, we intended to study the effect and related-mechanism of the proliferation, migration, invasion and induced apoptosis of anlotinib overcoming multidrug resistant colorectal cancer cells through in vitro experiments. Methods: Cell viability was determined by MTT assays and the resistant index was calculated. Colony formation and PI/RNase Staining were used for testing the proliferation of resistant cells. DAPI staining and Annexin V-FITC/PI staining were used to detect cell apoptosis. Migration and invasion were examined by transwell. Protein expression and activation of PI3K/AKT pathway were detected by western blot. LY294002 was used to verify whether anlotinib overcomes the drug-resistance of CRC cells by inactivating the PI3K/AKT pathway. Results: The results showed that the HCT-8/5-FU cells were resistant to multiple chemotherapy drugs (5-FU, ADM and DDP). Anlotinib significantly inhibited the cell viability, proliferation, migration, invasion and induced the cell apoptosis. Moreover, anlotinib downregulated the expression of survivin, cyclin D1, CDK4, caspase-3, Bcl-2, MMP-2, MMP-9, vimentin and N-cadherin, but up-regulated cleaved-caspase-3, Bax and E-cadherin and blocked the activity of the PI3K/AKT in HCT-8/5-FU cells. We found anlotinib and LY294002 overcame the drug resistance of HCT-8/5-FU cells by reducing the expression of PI3K/p-AKT. Conclusions: Anlotinib inhibited the proliferation, migration, invasion and induced apoptosis of HCT-8/5-FU cells, and the mechanisms may be that anlotinib conquered multidrug resistance of colorectal cancer cells via inactivating of PI3K/AKT pathway.

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Coptidis rhizoma Induces Apoptosis in Human Colorectal Cancer Cells SNU-C4

The American Journal of Chinese Medicine ◽

10.1142/s0192415x0400248x ◽

2004 ◽

Vol 32 (06) ◽

pp. 873-882 ◽

Cited By ~ 12

Author(s):

Youn Jung Kim ◽

Soon Ah Kang ◽

Mee Suk Hong ◽

Hae Jeong Park ◽

Mi-Ja Kim ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Death ◽

Cancer Cells ◽

Caspase 3 ◽

Apoptotic Cell ◽

Terminal Deoxynucleotidyl Transferase ◽

Human Colorectal Cancer ◽

Colorectal Cancer Cells ◽

Coptidis Rhizoma ◽

Human Colorectal Cancer Cells

Coptidis rhizoma has been used as traditional herb medicine in gastrointestinal disorders in the Eastern Asia. We investigated whether the anticancer effects of the C. rhizoma induced apoptosis on human colorectal cancer cells SNU-C4. The cytotoxic effect of C. rhizoma was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. To determine apoptotic cell death, 4,6-diamidino-2-phenylindole (DAPI) staining, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay, reverse transcription-polymerase chain reaction (RT-PCR) and caspase-3 enzyme assay were performed. In this study, C. rhizoma treatment (100 μg/ml) revealed typical morphological apoptotic features. Additionally, C. rhizoma treatment (100 μg/ml) increased levels of BAX and CASPASE-3, and decreased levels of BCL-2. Caspase-3 enzyme activity by treatment of C. rhizoma (100 μg/ml) also significantly increased compared to the control (p<0.05). These data indicate that C. rhizoma caused cell death by apoptosis through caspase pathways on human colorectal cancer cells SNU-C4.

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Sodium butyrate induces DRP1-mediated mitochondrial fusion and apoptosis in human colorectal cancer cells

Mitochondrion ◽

10.1016/j.mito.2013.10.004 ◽

2014 ◽

Vol 16 ◽

pp. 55-64 ◽

Cited By ~ 43

Author(s):

Dhanir Tailor ◽

Eun-Ryeong Hahm ◽

Raosaheb K. Kale ◽

Shivendra V. Singh ◽

Rana P. Singh

Keyword(s):

Colorectal Cancer ◽

Cancer Cells ◽

Sodium Butyrate ◽

Mitochondrial Fusion ◽

Human Colorectal Cancer ◽

Colorectal Cancer Cells ◽

Human Colorectal Cancer Cells

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Activation of CXCL12/CXCR4 renders colorectal cancer cells less sensitive to radiotherapy via up-regulating the expression of survivin

Experimental Biology and Medicine ◽

10.1177/1535370216675068 ◽

2016 ◽

Vol 242 (4) ◽

pp. 429-435 ◽

Cited By ~ 12

Author(s):

Dawei Wang ◽

Chengbin Jiao ◽

Yanli Zhu ◽

Deshen Liang ◽

Ming Zao ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Death ◽

Cancer Cells ◽

Caspase 3 ◽

Underlying Mechanism ◽

Caspase 9 ◽

Colorectal Cancer Cells ◽

Induced Apoptosis ◽

Common Malignancy ◽

Cxcr4 Axis

Colorectal cancer is the most common malignancy of the gastrointestinal tract. Surgical treatment combined with radiotherapy is the main treatment course for colorectal cancer; nevertheless, radio-resistance is commonly encountered during the treatment course and seriously influences the therapeutic efficacy. We tested the hypothesis that the CXCL12/CXCR4 axis is closely related to radiotherapy sensitivity in colorectal cancer cells. Here, we found that the decrease in cell viability and the increase in cell death induced by radiotherapy were attenuated by CXCL12 treatment, and the inhibition of CXCR4 promoted colorectal cancer cells to be more sensitive to radiotherapy. We also examined the critical roles of CXCL12/CXCR4 in cell survival and found that radiotherapy induced Bax expression and facilitated the activity of caspase-3 and caspase-9, which were reversed by CXCL12 treatment. Cell apoptosis was enhanced by the inhibition of CXCR4 under radiotherapy conditions. Furthermore, treatment with CXCL12 resulted in an increased expression of survivin, and the inhibitory roles of CXCL12 in radiotherapy-induced apoptosis were mitigated by survivin knockdown. These results indicate that CXCL12/CXCR4 protects colorectal cancer cells against radiotherapy via survivin, implying an important underlying mechanism of resistance to radiotherapy during colorectal cancer therapy.

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Sensitization of FOLFOX-resistant colorectal cancer cells via the modulation of a novel pathway involving protein phosphatase 2A

10.1101/2021.07.21.453259 ◽

2021 ◽

Author(s):

Satya Narayan ◽

Asif Raza ◽

Iqbal Mahmud ◽

Nayeong Koo ◽

Timothy Garrett ◽

...

Keyword(s):

Colorectal Cancer ◽

Protein Synthesis ◽

Cancer Cells ◽

Small Molecule ◽

Protein Phosphatase ◽

Caspase 3 ◽

Protein Phosphatase 2A ◽

Global Protein Synthesis ◽

Colorectal Cancer Cells ◽

Phosphatase 2A

The treatment of colorectal cancer (CRC) with FOLFOX shows some efficacy, but these tumors quickly develop resistance to this treatment. We have observed an increased phosphorylation of AKT1/mTOR/4EBP1 and levels of p21 in FOLFOX-resistant CRC cells. We have identified a small molecule, NSC49L, that stimulates protein phosphatase 2A (PP2A) activity, downregulates the AKT1/mTOR/4EBP1-axis, and inhibits p21 translation. We have provided evidence that NSC49L- and TRAIL-mediated sensitization is synergistically induced in p21-knockdown CRC cells, which is reversed in p21-overexpressing cells. p21 binds with procaspase 3 and prevents activation of caspase 3. We have shown that TRAIL induces apoptosis through the activation of caspase 3 by NSC49L-mediated downregulation of p21 translation, and thereby cleavage of procaspase 3 into caspase 3. NSC49L does not affect global protein synthesis. These studies provide a mechanistic understanding of NSC49L as a PP2A agonist, and how its combination with TRAIL sensitizes FOLFOX-resistant CRC cells.

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Augmentation of the anticancer effects of proteasome inhibitors by combination with sodium butyrate in human colorectal cancer cells

Experimental and Therapeutic Medicine ◽

10.3892/etm_00000106 ◽

2010 ◽

Vol 1 (4) ◽

pp. 675-693 ◽

Cited By ~ 8

Author(s):

M.S.I. ABAZA

Keyword(s):

Colorectal Cancer ◽

Cancer Cells ◽

Sodium Butyrate ◽

Proteasome Inhibitors ◽

Human Colorectal Cancer ◽

Anticancer Effects ◽

Colorectal Cancer Cells ◽

Human Colorectal Cancer Cells

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α-Linolenic and γ-linolenic acids exercise differential antitumor effects on HT-29 human colorectal cancer cells

Toxicology Research ◽

10.1093/toxres/tfaa046 ◽

2020 ◽

Vol 9 (4) ◽

pp. 474-483 ◽

Cited By ~ 1

Author(s):

María José González-Fernández ◽

Ignacio Ortea ◽

José Luis Guil-Guerrero

Keyword(s):

Colorectal Cancer ◽

Cancer Cells ◽

Linolenic Acid ◽

Caspase 3 ◽

Colorectal Cancer Cell Line ◽

Human Colorectal Cancer ◽

Antitumor Effects ◽

Colorectal Cancer Cells ◽

Microscopy Images ◽

Ht 29

Abstract α-Linolenic acid (ALA, 18:3n-3) and γ-gamma linolenic acid (GLA, 18:3n-6) are polyunsaturated fatty acids (PUFA) that improve the human health. The present study focused on testing the in vitro antitumor actions of pure ALA and GLA on the HT-29 human colorectal cancer cell line. Cell viability was checked by MTT ((3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) test, cell membrane damage by the lactate dehydrogenase assay, apoptosis was tested by both caspase-3 activity trial and transmission electron microscopy images, and protein composition was analyzed by quantitative proteomics analysis. MTT test revealed IC50 values of 230 and 255 μM for ALA and GLA, respectively, at 72 h. After 24 h of incubation, both ALA and GLA induced apoptosis on HT-29 colorectal cancer cells according to the caspase-3 assay and microscopy images. SWATH/MS analysis evidenced that ALA significantly affected the mitochondrial protein import pathway and the citric acid cycle pathway, while GLA did not significantly affect any particular pathway. In summary, both ALA and GLA showed concentration-dependent inhibitory effects on HT-29 cells viability and induced cell death by apoptosis. ALA significantly affected cellular pathways, while GLA does not have specific actions on either pathway. Both n-3 and n-6 C18 PUFA are bioactive food components useful in the colorectal cancer prevention.

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RNA Sequencing Analysis of Molecular Basis of Sodium Butyrate-Induced Growth Inhibition on Colorectal Cancer Cell Lines

BioMed Research International ◽

10.1155/2019/1427871 ◽

2019 ◽

Vol 2019 ◽

pp. 1-11 ◽

Cited By ~ 1

Author(s):

Qianwen Zhou ◽

Guiqin Li ◽

Siyu Zuo ◽

Wenjing Zhu ◽

Xiaoqin Yuan

Keyword(s):

Colorectal Cancer ◽

Cell Death ◽

Cancer Cells ◽

Rna Sequencing ◽

Differentially Expressed Genes ◽

Sodium Butyrate ◽

Differentially Expressed ◽

Sequencing Analysis ◽

Inhibition Of Proliferation ◽

Colorectal Cancer Cells

Butyrate is a short-chain fatty acid decomposed from dietary fiber and has been shown to have effects on inhibition of proliferation but induction of apoptosis in colorectal cancer cells. However, clinical trials have yielded ambiguous outcomes with regard to its antitumor activities. In this study, we aimed to explore the molecular mechanisms underlying the sensitivity of colorectal cancer cells to sodium butyrate (NaB). RNA sequencing was used to establish the whole-transcriptome profile in NaB-treated versus untreated colorectal cancer cells. Differentially expressed genes were bioinformatically analyzed to predict their possible involvement in NaB-triggered cell death, and the expression of eight dysregulated genes was validated by quantitative real-time PCR. We found that there were a total of 7192 genes (5720 upregulated and 1472 downregulated, fold-change ≥ 2 or ≤ 0.5 for upregulation or downregulation, q-value < 0.05) differentially expressed in NaB-treated cells as compared with the untreated controls. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis demonstrated that the differentially expressed genes were enriched in DNA replication, cell cycle, homologous recombination, pyrimidine metabolism, mismatch repair, and other signaling pathways and may take part in NaB-induced cell death. Among the identified factors, the MCM2-7 complex might be a target of NaB. Our findings provide an important basis for further studies of the complicate network that might regulate sensitivity of colorectal cancer cells to NaB.

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Expression of β-catenin is regulated by PI-3 kinase and sodium butyrate in colorectal cancer cells

International Journal of Molecular Medicine ◽

10.3892/ijmm.17.1.69 ◽

2006 ◽

Author(s):

Jolana Turecková ◽

Dana Kucerová ◽

Martina Vojtechová ◽

Eva Sloncová ◽

Zdena Tuhácková

Keyword(s):

Colorectal Cancer ◽

Cancer Cells ◽

Sodium Butyrate ◽

Colorectal Cancer Cells

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