Apoptotic pathways and stemness in the colorectal epithelium and lamina propria mucosae during the human embryogenesis and carcinogenesis

Sedlar, Ivana Tica; Petričević, Joško; Saraga-Babić, Mirna; Pintarić, Irena; Vukojević, Katarina

doi:10.1016/j.acthis.2016.08.004

Cited by 4 publications

(2 citation statements)

References 58 publications

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“…The oral administration of capsaicin in this study markedly induced the expression of apoptosis-related genes in the colonic mucosa, including Casp4, Sp1, Aifm1 and Dffb. Capsaicin-induced apoptosis has been reported to cause ER calcium release and to increase the transcriptional activation of pro-apoptotic genes (O'Neill et al 2012;Srivastava 2013;Thomas et al 2011) such as Aifm, an important effector for caspase-independent cell death (Tica Sedlar et al 2016). Aifm encodes an apoptosis-inducing factor (AIF) that functions as an oxidoreductase in the inner mitochondrial membrane (Sun et al 2016).…”

Section: Discussionmentioning

confidence: 99%

Capsaicin reduces genotoxicity, colonic cell proliferation and preneoplastic lesions induced by 1,2-dimethylhydrazine in rats

Caetano

Tablas

Pereira

et al. 2018

Toxicology and Applied Pharmacology

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Capsaicin (8-Methyl-N-vanillyl-(trans)-6-nonenamide) is the major pungent ingredient found in chili peppers consumed worldwide. Most reports on capsaicin potential carcinogenicity have yielded inconsistent findings. Some studies have shown that capsaicin exerts anti-proliferative and pro-apoptotic effects on different cancer cell lines, while others have reported an association between capsaicin at high doses with mutagenicity and carcinogenicity. Thus, this study aimed at assessing the effects of capsaicin administration on 1,2-dimethyl-hydrazine (DMH)-induced colon carcinogenesis in male Wistar rats. Our results show that capsaicin administration, before and during carcinogen exposure, modified DMH-induced cytotoxicity and genotoxicity, promoting anti-proliferative and pro-apoptotic responses through the expression of the genes involved in apoptosis, cell cycle suppression and cell/tissue differentiation. Furthermore, capsaicin reduced aberrant crypt foci (ACF) number and multiplicity, although there were no differences in tumor incidence and multiplicity among the groups. Taken together, the results suggest that capsaicin may have a preventive effect against DMH-induced colorectal carcinogenesis.

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Section: Discussionmentioning

confidence: 99%

Capsaicin reduces genotoxicity, colonic cell proliferation and preneoplastic lesions induced by 1,2-dimethylhydrazine in rats

Caetano

Tablas

Pereira

et al. 2018

Toxicology and Applied Pharmacology

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“…Colorectal CSCs, which display unlimited self-renewal ability [5], are responsible for tumor relapse [6-8]. Colorectal CSCs are characterized by the expression of biomarkers; LGR5 + [9], EphB2 high [10], CD44v6 + [11], ALDH + [12] and OCT-4 + [13]. …”

Section: Introductionmentioning

confidence: 99%

Reduction of NANOG Mediates the Inhibitory Effect of Aspirin on Tumor Growth and Stemness in Colorectal Cancer

Wang¹,

Liu²,

Wang³

et al. 2017

Cell Physiol Biochem

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Background/Aims: Cancer stem cells (CSCs) are considered to be responsible for tumor relapse and metastasis, which serve as a potential therapeutic target for cancer. Aspirin has been shown to reduce cancer risk and mortality, particularly in colorectal cancer. However, the CSCs-suppressing effect of aspirin and its relevant mechanisms in colorectal cancer remain unclear. Methods: CCK8 assay was employed to detect the cell viability. Sphere formation assay, colony formation assay, and ALDH1 assay were performed to identify the effects of aspirin on CSC properties. Western blotting was performed to detect the expression of the stemness factors. Xenograft model was employed to identify the anti-cancer effects of aspirin in vivo. Unpaired Student t test, ANOVA test and Kruskal-Wallis test were used for the statistical comparisons. Results: Aspirin attenuated colonosphere formation and decreased the ALDH1 positive cell population of colorectal cancer cells. Aspirin inhibited xenograft tumor growth and reduced tumor cells stemness in nude mice. Consistently, aspirin decreased the protein expression of stemness-related transcription factors, including c-Myc, OCT4 and NANOG. Suppression of NANOG blocked the effect of aspirin on sphere formation. Conversely, ectopic expression of NANOG rescued the aspirin-repressed sphere formation, suggesting that NANOG is a key downstream target. Moreover, we found that aspirin repressed NANOG expression in protein level by decreasing its stability. Conclusion: We have provided new evidence that aspirin attenuates CSC properties through down-regulation of NANOG, suggesting aspirin as a promising therapeutic agent for colorectal cancer treatment.

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Immunohistochemical evaluation of bcl-2, ER-alpha, caspase -3, -8, -9, PCNA and Ki-67 expressions in canine mammary carcinomas

Aydoğan

Özmen

Halıgür

et al. 2018

Biotechnic & Histochemistry

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We investigated the expression of bcl-2, estrogen receptor alpha (ER-alpha), caspase-3, -8, -9, proliferating cell nuclear antigen (PCNA) and Ki-67 in canine mammary carcinomas. We used 65 paraffin embedded and re-diagnosed archival canine mammary tumor samples to which we applied the routine streptavidin-biotin-peroxidase technique. Seventeen cases were re-diagnosed as tubulopapillary carcinoma, 31 were re-diagnosed as complex carcinoma and 17 were re-diagnosed as carcinosarcoma. Differences of expression of bcl-2 and PCNA were statistically significant according to tumor type. Differences in expression of ER-alpha, caspase-3, -8, -9 and Ki-67 were not statistically significant. Differences of expression of bcl-2 and PCNA were statistically significant compared to ER-alpha, caspase-3, -8, -9 and Ki-67 in carcinosarcomas. We report the prognostic significance of bcl-2 and PCNA expression in canine mammary carcinosarcomas.

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Apoptotic pathways and stemness in the colorectal epithelium and lamina propria mucosae during the human embryogenesis and carcinogenesis

Cited by 4 publications

References 58 publications

Capsaicin reduces genotoxicity, colonic cell proliferation and preneoplastic lesions induced by 1,2-dimethylhydrazine in rats

Capsaicin reduces genotoxicity, colonic cell proliferation and preneoplastic lesions induced by 1,2-dimethylhydrazine in rats

Reduction of NANOG Mediates the Inhibitory Effect of Aspirin on Tumor Growth and Stemness in Colorectal Cancer

Immunohistochemical evaluation of bcl-2, ER-alpha, caspase -3, -8, -9, PCNA and Ki-67 expressions in canine mammary carcinomas

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