APTM, a Thiophene Heterocyclic Compound, Inhibits Human Colon Cancer HCT116 Cell Proliferation Through p53-Dependent Induction of Apoptosis

Liao, Xinyang; Huang, Jiajun; Wu, Lin; Long, Zhe; Xie, Yu; Ma, Wenzhe

doi:10.1089/dna.2017.3962

Cited by 8 publications

(3 citation statements)

References 39 publications

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“…KEGG enrichment analysis of DEGs in cell transcriptome sequencing showed that FCN3 upregulation was associated with the p53 signaling pathway (Fig. 2B), which was widely reported to be involved in cell proliferation, apoptosis (20)(21)(22). Meanwhile, Gene set enrichment analysis (GSEA) was performed with TCGA data and the results indicated that the high expression of FCN3 was closely related to apoptosis (Fig.…”

Section: Fcn3 Overexpression Promoted Apoptosis and Suppressed Prolif...mentioning

confidence: 95%

FCN3 inhibits the progression of hepatocellular carcinoma by suppressing SBDS-mediated blockade of the p53 pathway

Ma¹,

Liu²,

Wen³

et al. 2023

Int. J. Biol. Sci.

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Hepatocellular carcinoma (HCC) is the third-leading cause of cancer deaths globally. Although considerable progress has been made in the treatment, clinical outcomes of HCC patients are still poor. Therefore, it is necessary to find novel prognostic factors upon which prevention and treatment strategies can be formulated. Ficolin-3 (FCN3) protein is a member of the human ficolin family. It activates complement through pathways associated with mannose-binding lectin-associated serine proteases. Herein, we identified that FCN3 was downregulated in HCC tissues and decreased FCN3 expression was closely related to poor prognosis. Overexpression of FCN3 induced apoptosis and inhibited cell proliferation via the p53 signaling pathway. Mechanistically, FCN3 modulated the nuclear translocation of eukaryotic initiation factor 6 (EIF6) by binding ribosome maturation factor (SBDS), which induced ribosomal stress and activation of the p53 pathway. In addition, Y-Box Binding Protein 1 (YBX1) involved in the transcription and translation level regulation of FCN3 to SBDS. Besides, a negative feedback loop in the downstream of FCN3 involving p53, YBX1 and SBDS was identified.

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Section: Fcn3 Overexpression Promoted Apoptosis and Suppressed Prolif...mentioning

confidence: 95%

FCN3 inhibits the progression of hepatocellular carcinoma by suppressing SBDS-mediated blockade of the p53 pathway

Ma¹,

Liu²,

Wen³

et al. 2023

Int. J. Biol. Sci.

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“… 32 The oligomerization of these proteins on the mitochondrial outer membrane increases its permeability and triggers the discharge of apoptosis-inducing mediators such as cytochrome C, Smac, and other proteins that promote caspase activity to kill the cell through the intrinsic apoptotic pathway. 33 , 34 …”

Section: Resultsmentioning

confidence: 99%

“…32 The oligomerization of these proteins on the mitochondrial outer membrane increases its permeability and triggers the discharge of apoptosisinducing mediators such as cytochrome C, Smac, and other proteins that promote caspase activity to kill the cell through the intrinsic apoptotic pathway. 33,34 In an attempt to understand the molecular mechanism underlying the anticancer activity of compound 1, the expression of Bax, Bcl-2, and p53 was examined by Western blotting in HCT-116 cells that were more sensitive to compound 1 compared to MCF-7 cells as inferred from the MTT cell viability assay. HCT-116 cells were subjected to various doses of compound 1 for 48 hours and results are shown in Fig.…”

Section: Western Blot Analysismentioning

confidence: 99%

Molecular properties prediction, anticancer and anti-inflammatory activities of some pyrimido[1,2-b]pyridazin-2-one derivatives

Zeiz,

Kawtharani,

Elmasri

et al. 2023

Bioimpacts

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Introduction: The anticancer and anti-inflammatory activities of a novel series of eleven pyrimido[1,2-b]pyridazin-2-one analogues substituted at position 7 were assessed in the current study. Methods: The physicochemical characteristics were studied using MolSoft software. The antiproliferative activity was investigated by MTT cell viability assay, and cell cycle analysis elucidated the antiproliferative mechanism of action. Western blot analysis examined the expression levels of key pro-apoptotic (Bax, p53) and pro-survival (Bcl-2) proteins. The anti-inflammatory activity was assessed by measuring the production levels of nitric oxide in RAW264.7 cells, and the expression levels of COX-2 enzyme in LPS-activated THP-1 cells. In addition, the gene expression of various pro-inflammatory cytokines (IL-6, IL-8, IL-1β, TNF-α) and chemokines (CCL2, CXCL1, CXCL2, CXCL3) was assessed by RT-qPCR. Results: Compound 1 bearing a chlorine substituent displayed the highest cytotoxic activity against HCT-116 and MCF-7 cancer cells where IC50 values of 49.35 ± 2.685 and 69.32 ± 3.186 µM, respectively, were achieved. Compound 1 increased the expression of pro-apoptotic proteins p53 and Bax while reducing the expression of pro-survival protein Bcl-2. Cell cycle analysis revealed that compound 1 arrested cell cycle at the G0/G1 phase. Anti-inflammatory assessments revealed that compound 1 displayed the strongest inhibitory activity on NO production with IC50 of 29.94 ± 2.24 µM, and down-regulated the expression of COX-2. Compound 1 also induced a statistically significant decrease in the gene expression of various cytokines and chemokines. Conclusion: These findings showed that the pyrimidine derivative 1 displayed potent anti-inflammatory and anticancer properties in vitro, and can be selected as a lead compound for further investigation.

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New 5, 6, 7, 8‐Tetrahydro‐Isoquinolines Bearing 2‐Nitrophenyl Group Targeting RET Enzyme: Synthesis, Anticancer Activity, Apoptotic Induction and Cell Cycle Arrest

Saddik,

Bakhite,

Hassanien

et al. 2024

Chemistry & Biodiversity

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In this work, we synthesized new 5,6,7,8‐tetrahydroisoquinolines and 6,7,8,9‐tetrahydrothieno[2,3‐c]isoquinolines derivatives and the structures of these new compounds were confirmed with different spectroscopic techniques. Furthermore, the anticancer activities of these compounds were assessed against eight tumor cell lines and one normal human skin fibroblast cell line (HSF). Subsequently, IC50 values of the synthesized compounds were determined for two specific cancer cell lines. Compound 3 exhibited the most potent antiproliferative activity against the HEPG2 cell line, whereas compound 9c demonstrated superior efficacy against the HCT116 cell line. Moreover, the mechanism of action for compound 3 on HEPG2 cells using flow cytometry and Annexin V‐FITC apoptosis analysis was studied. Compound 3 caused cell cycle arrest at the G2/M with a 50‐fold increase in apoptosis of the HEPG2 cell line. Finally, a molecular docking study was conducted to assess the inhibitory potential of compounds 3 and 7 against the RET enzyme. Results indicated that compounds 3 and 7 bind to the RET enzyme with binding energies of ‐5.2 and ‐5.6 kcal/mol, respectively. While these values suggest inhibitory activity, they are less potent than the standard inhibitor, alectinib, which exhibits a binding energy of ‐7.2 kcal/mol.

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APTM, a Thiophene Heterocyclic Compound, Inhibits Human Colon Cancer HCT116 Cell Proliferation Through p53-Dependent Induction of Apoptosis

Cited by 8 publications

References 39 publications

FCN3 inhibits the progression of hepatocellular carcinoma by suppressing SBDS-mediated blockade of the p53 pathway

FCN3 inhibits the progression of hepatocellular carcinoma by suppressing SBDS-mediated blockade of the p53 pathway

Molecular properties prediction, anticancer and anti-inflammatory activities of some pyrimido[1,2-b]pyridazin-2-one derivatives

New 5, 6, 7, 8‐Tetrahydro‐Isoquinolines Bearing 2‐Nitrophenyl Group Targeting RET Enzyme: Synthesis, Anticancer Activity, Apoptotic Induction and Cell Cycle Arrest

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