scholarly journals HSP90 Inhibitors, Geldanamycin and Radicicol, Enhance Fisetin-Induced Cytotoxicity via Induction of Apoptosis in Human Colonic Cancer Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Ming-Shun Wu ◽  
Gi-Shih Lien ◽  
Shing-Chuan Shen ◽  
Liang-Yo Yang ◽  
Yen-Chou Chen
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Caspase 3 ◽  
P53 Protein ◽  
Colon Cancer Cells ◽  
Hsp90 Inhibitors ◽  
Dna Ladder ◽  
Human Colon Cancer ◽  
Bax Protein

We revealed the cytotoxic effect of the flavonoid, fisetin (FIS), on human COLO205 colon cancer cells in the presence and absence of the HSP90 inhibitors, geldanamycin (GA) and radicicol (RAD). Compared to FIS treatment alone of COLO205 cells, GA and RAD significantly enhanced FIS-induced cytotoxicity, increased expression of cleaved caspase-3 and the PAPR protein, and produced a greater density of DNA ladder formation. GA and RAD also reduced the MMPs with induction of caspase-9 protein cleavage in FIS-treated COLO205 cells. Increased caspase-3 and -9 activities were detected in COLO205 cells treated with FIS+GA or FIS+RAD, and the intensity of DNA ladder formation induced by FIS+GA was reduced by adding the caspase-3 inhibitor, DEVD-FMK. A decrease in Bcl-2 but not Bcl-XL or Bax protein by FIS+GA or FIS+RAD was identified in COLO205 cells by Western blotting. A reduction in p53 protein with increased ubiquitin-tagged proteins was observed in COLO205 cells treated with FIS+GA or FIS+RAD. Furthermore, GA and RAD reduced the stability of the p53 protein in COLO205 cells under FIS stimulation. The evidence supports HSP90 inhibitors possibly sensitizing human colon cancer cells to FIS-induced apoptosis, and treating colon cancer by combining HSP90 inhibitors with FIS deserves further in vivo study.

scholarly journals In Vitro and in Vivo antitumor activity and the mechanism of siphonodictyal B in human colon cancer cells

2019 ◽  
Vol 8 (12) ◽  
pp. 5662-5672 ◽  
Author(s):  
Sonoko Chikamatsu ◽  
Ken Saijo ◽  
Hiroo Imai ◽  
Koichi Narita ◽  
Yoshifumi Kawamura ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Antitumor Activity ◽  
Cancer Cells ◽  
Human Colon ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
In Vivo Antitumor Activity ◽  
Human Colon Cancer Cells

scholarly journals NF-κB maintains the stemness of colon cancer cells by downregulating miR-195-5p/497–5p and upregulating MCM2

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Longgang Wang ◽  
Jinxiang Guo ◽  
Jin Zhou ◽  
Dongyang Wang ◽  
Xiuwen Kang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Human Colon ◽  
Colon Cancer Cells ◽  
Tumor Models ◽  
Human Colon Cancer ◽  
Subcutaneous Tumor

Abstract Background Colon cancer represents one of the leading causes of gastrointestinal tumors in industrialized countries, and its incidence appears to be increasing at an alarming rate. Accumulating evidence has unveiled the contributory roles of cancer stem cells (CSCs) in tumorigenicity, recurrence, and metastases. The functions of NF-kappa B (NF-κB) activation on cancer cell survival, including colon cancer cells have encouraged us to study the role of NF-κB in the maintenance of CSCs in colon cancer. Methods Tumor samples and matched normal samples were obtained from 35 colon cancer cases. CSCs were isolated from human colon cancer cell lines, where the stemness of the cells was evaluated by cell viability, colony-forming, spheroid-forming, invasion, migration, and apoptosis assays. NF-κB activation was then performed in subcutaneous tumor models of CSCs by injecting lipopolysaccharides (LPS) i.p. Results We found that NF-κB activation could reduce the expression of miR-195-5p and miR-497-5p, where these two miRNAs were determined to be downregulated in colon cancer tissues, cultured colon CSCs, and LPS-injected subcutaneous tumor models. Elevation of miR-195-5p and miR-497-5p levels by their specific mimic could ablate the effects of NF-κB on the stemness of colon cancer cells in vivo and in vitro, suggesting that NF-κB could maintain the stemness of colon cancer cells by downregulating miR-195-5p/497–5p. MCM2 was validated as the target gene of miR-195-5p and miR-497-5p in cultured colon CSCs. Overexpression of MCM2 was shown to restore the stemness of colon cancer cells in the presence of miR-195-5p and miR-497-5p, suggesting that miR-195-5p and miR-497-5p could impair the stemness of colon cancer cells by targeting MCM2 in vivo and in vitro. Conclusions Our work demonstrates that the restoration of miR-195-5p and miR-497-5p may be a therapeutic strategy for colon cancer treatment in relation to NF-κB activation.

scholarly journals Identification of a thymidylate synthase ribonucleoprotein complex in human colon cancer cells.

1994 ◽  
Vol 14 (1) ◽  
pp. 207-213 ◽  
Author(s):  
E Chu ◽  
D M Voeller ◽  
K L Jones ◽  
T Takechi ◽  
G F Maley ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Thymidylate Synthase ◽  
Translational Regulation ◽  
Direct Interaction ◽  
Human Colon ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Human Colon Cancer Cells

Translation of thymidylate synthase (TS) mRNA is controlled by its own protein product, TS, in an autoregulatory manner. Direct binding of TS protein to two different cis-acting elements on the TS mRNA is associated with this translational regulation. In this study, an immunoprecipitation-reverse transcription-PCR technique was used to identify a TS ribonucleoprotein (RNP) complex in cultured human colon cancer cells. Using antibodies specific for TS protein, we show that TS is complexed in vivo with its own TS RNA. Furthermore, evidence demonstrating a direct interaction between the mRNA of the nuclear oncogene c-myc and TS protein is presented.

Effect of polyamide nanoparticles on apoptosis of colon cancer cells induced by survivin antisense oligonucleotide

2020 ◽  
Vol 10 (9) ◽  
pp. 1573-1580
Author(s):  
Yongqiang Xu ◽  
Weibiao Ye ◽  
Chan Zhou ◽  
Yuling Li ◽  
Jianfang He
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
P38 Mapk ◽  
Caspase 3 ◽  
Human Colon ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Significant Difference ◽  
Microfilament System ◽  
Human Colon Cancer Cells

In this study, we aimed to observe the effect of polyamidoamine (PAMAM) liposomes on the apoptosis of human colon cancer cells induced by survivin antisense oligonucleotides (ASODNs). PAMAM liposomes and PAMAM were mixed with survivin ASODNs to obtain antisense gene transfection complexes. In addition, the zeta potentials and encapsulation rates of the complexes were measured. The two gene-containing complexes were transfected into HT-29 colon cancer cells to observe changes in cell morphology, detect the inhibitory effect on tumor cells and changes in apoptosis, and observe changes in the cytoskeleton microfilament system using laser confocal microscopy. Caspase-3 activity in the cells was determined using a kinase activity assay, and p38 mitogen-activated protein kinase (p38 MAPK) activity in the cells was measured using immunoprecipitation analysis. The results showed that the zeta potential of the PAMAM liposome-survivin-ASODN complex was higher than that of the PAMAM-survivin-ASODN complex (P < 0.05). There was no significant difference in the gene encapsulation rates between the two complexes (P > 0.05). PAMAM liposomes may efficiently deliver survivin ASODNs to human colon cancer cells, reduce the expression of survivin protein and at the same time induce G2/M phase arrest in cells, and activate caspase-3 by activating p38 MAPK. Cleavage of caspase-3 destroys the structure of the intracellular skeletal microfilament system, finally resulting in apoptosis of colon cancer cells.

scholarly journals Evaluation of Anti-Tumorigenic Effects of Diosmetin against Human Colon Cancer Xenografts in Athymic Nude Mice

Molecules ◽  
2019 ◽  
Vol 24 (14) ◽  
pp. 2522 ◽  
Author(s):  
Sanaz Koosha ◽  
Zahurin Mohamed ◽  
Ajantha Sinniah ◽  
Mohammed A. Alshawsh
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Nude Mice ◽  
Human Colon ◽  
Tumor Growth Rate ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Apoptotic Protein ◽  
Hct 116

Colon cancer is the third most common type of cancer in the world. Diosmetin (Dis), a natural O-methylated flavone, has been reported to have anti-cancer effects against different types of cancer. Although the mechanisms of action of Dis against several cancer cell lines are well reported, in vivo anti-tumorigenesis properties of this compound are still obscure. Therefore, this study aimed to investigate the anti-tumorigenesis properties of Dis against HCT-116 colon cancer xenografts in nude mice. HCT-116 colon cancer cells were injected in NCr nu/nu nude mice and treatment with Dis was initiated after the tumor volumes reached 100 mm3 and continued for four weeks. On the sacrificing date nude mice treated with 100 mg/kg of Dis showed significant lower tumor volume (264 ± 238.3 mm3) as compared to the untreated group (1428.8 ± 459.6 mm3). Anti-apoptotic Bcl-2 protein was significantly downregulated, while apoptotic protein (Bax) was significantly overexpressed in nude mice treated with 100 mg/kg Dis as compared to untreated mice. In conclusion, our in vivo results indicate that Dis significantly reduces tumor growth rate of HCT-116 colon cancer cells in nude mice at a dose of 100 mg/kg, and has no toxic effects in ICR mice up to 2000 mg/kg.

Validation of TPX2 as a novel prognostic marker for malignant progression and metastasis of colon cancer.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 442-442 ◽  
Author(s):  
Ping Wei ◽  
Dawei Li ◽  
Ye Xu ◽  
Sanjun Cai
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Human Colon ◽  
Clinical Staging ◽  
Migration And Invasion ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
A Genome

442 Background: We previously identified aberrant overexpression of TPX2 in colon cancer by using a genome-wide gene expression profiling analysis. Here, we aimed to investigate its expression pattern, clinical significance, and biological function in colon cancer. Methods: The expression of TPX2 was analyzed in human colon cancer cell lines and tumor samples. The effect of TPX2 on cell proliferation, tumorigenesis and metastasis was examined in vitro and in vivo. Results: Overexpression of TPX2 was found in metastatic lesion of colon cancer, significantly higher than primary cancererous tissue and normal colon mucosa. Overexpression of TPX2 was significantly associated with the clinical staging, vessel invasion and metastasis. In survival analyses, patients with TPX2 expression had worse overall survival and metastasis free survival, suggesting that deregulation of TPX2 may contribute to the metastasis of colon cancer. Consistently, Silencing TPX2 inhibited proliferation and tumorigenicity of colon cancer cells both in vitro and in vivo. Strikingly, we found that TPX2 knockdown significantly attenuated the migration and invasion ability of colon cancer cells, which was further shown to be mechanistically associated with AKT mediated MMP9 activity. Conclusions: These findings suggest that TPX2 plays an important role in promoting tumorigenesis and metastasis of human colon cancer and may represent a novel prognostic biomarker and therapeutic target for the disease.

Diallyl sulfide induces apoptosis in Colo 320 DM human colon cancer cells: involvement of caspase-3, NF-κB, and ERK-2

2008 ◽  
Vol 311 (1-2) ◽  
pp. 157-165 ◽  
Author(s):  
Narayanan Sriram ◽  
Srinivasan Kalayarasan ◽  
Pandurangan Ashokkumar ◽  
Ananthasadagopan Sureshkumar ◽  
Ganapasam Sudhandiran
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Caspase 3 ◽  
Human Colon ◽  
Colon Cancer Cells ◽  
Diallyl Sulfide ◽  
Human Colon Cancer ◽  
Human Colon Cancer Cells
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