Implications of cleaved caspase 3 and AIF expression in colorectal cancer based on patient age

Perraud, Aurï¿1⁄2lie

doi:10.3892/or.2012.1737

Cited by 6 publications

(4 citation statements)

References 15 publications

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“…Caspase-3, the most critical apoptosis performer downstream of the caspase cascade, is known as the "death protease" (31). Previous studies have demonstrated that co-expression level of cleaved caspase-3 (cle-caspase-3) and caspase-3 might be a prognostic biomarker for cancer patients (32,33). This study demonstrates that QFG increased the expression of cle-caspase-3 in CRC tumor cells and induced apoptosis.…”

Section: Discussionmentioning

confidence: 54%

Qingjie Fuzheng Granules regulates cancer cell proliferation, apoptosis and tumor angiogenesis in colorectal cancer xenograft mice via Sonic Hedgehog pathway

Zhu¹,

Yang²,

Mu³

et al. 2020

J Gastrointest Oncol

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Background: Sonic Hedgehog (SHh) signaling pathway plays a critical role in cell proliferation, apoptosis, and tumor angiogenesis in various types of malignancies including colorectal cancer (CRC). Qingjie Fuzheng Granules (QFG) is a traditional Chinese medicinal formula, which has been clinically used in various cancer treatments, including CRC. In this study, we explored the potential molecular mechanisms of QFG treatment effects on CRC via the SHh pathway.Methods: A CRC HCT-116 xenograft mouse model was utilized for all experiments. Mice were treated with intra-gastric administration of 1 g/kg of QFG or saline 6 days a week for 28 days (4 weeks). Body weight, length and shortest diameter of the tumor were measured every 3 days. At the end of the treatment, the tumor weight was measured. TUNEL staining assays were used to detect tumor apoptosis. Western blot and immunohistochemistry (IHC) assays were used to detect the expression of relative proteins.Results: In our results, QFG inhibited the increase of tumor volume and weight, and exhibited no impact on mouse body weight. Furthermore, QFG significantly decreased the expression of SHh, Smo and Gli proteins, indicating the action of SHh signaling. Consequently, the expression of pro-proliferative survivin, Ki-67, Cyclin-D1 and CDK4 were decreased and expression of anti-proliferative p21 was increased. The pro-apoptotic Bax/Bcl-2 ratio, cle-caspase-3 and TUNEL-positive cell percentage in tumor tissues were increased. Meanwhile, the pro-angiogenic VEGF-A and VEGFR-2 expression was down-regulated.Conclusions: QFG inhibited CRC cell proliferation and promoted CRC cell apoptosis and tumor angiogenesis in vivo through the suppression of SHh pathway, suggesting that QFG could be a potential therapeutic drug for CRC.

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Section: Discussionmentioning

confidence: 54%

Qingjie Fuzheng Granules regulates cancer cell proliferation, apoptosis and tumor angiogenesis in colorectal cancer xenograft mice via Sonic Hedgehog pathway

Zhu¹,

Yang²,

Mu³

et al. 2020

J Gastrointest Oncol

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“…In this study, we found that treatments with FBR and is strongly associated with prolonged survival in male CRC patients [60]. Activated Casp3, which performs the cleavage of the poly (ADP-ribose) polymerase family, member 1 (PARP1) and induces cell apoptosis, is a useful strategy in colon cancer prevention and treatment [61]. In this study, we found that the dietary MCG-PC treatment significantly enhanced the activation of Casp3 in the colon tissue of CRC mice.…”

Section: Discussionmentioning

confidence: 91%

Dietary Mixed Cereal Grains Ameliorate the Azoxymethane and Dextran Sodium Sulfate-Induced Colonic Carcinogenesis in C57BL/6J Mice

Song¹,

Wang²,

Lee³

et al. 2019

Preprint

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The chemopreventive effects of various mixed cereal grain (MCG) samples on azoxymethane (AOM, 10 mg/kg) and dextran sulfate sodium (DSS, 2% w/v)-induced colorectal cancer (CRC) in C57BL/6J mice were studied. The main MCG preparation consisted of fermented brown rice (FBR), glutinous brown rice, glutinous Sorghum bicolor, glutinous Panicum miliaceum, Coix lacryma-jobi and black soybean at an appropriate mixing ratio. Other MCG preparations contained rice coated with 5% Phellinus linteus and 5% Curcuma longa (MGR-PC), or 10% Phellinus linteus (MCG-P), or 10% Curcuma longa (MCG-C). Consumption of dietary MCG-PC by CRC mice significantly increased colon length, decreased the ratio of colon weight to length, and reduced the number of colon tumors. Similar effects, although to a lower extent, were observed in CRC mice fed with MCG-P, followed by those fed with MCG-C, MCG, FBR or white rice (WR). MCG-PC significantly suppressed colonic neoplasia, and decreased the levels of various cytokines (tumor necrosis factor: Tnf, interleukin 1 beta: Il1b, interleukin 6: Il6, and interferon gamma: Ifng) in serum and colon tissue of the CRC mice. In addition, MCG-PC increased the mRNA expressions of tumor protein p53(Tp53) and cyclin-dependent kinase inhibitor 1A(Cdkn1a), activated pro-apoptotic caspase 3(Casp3), and reduced expression of both mRNA and protein of inducible inducible nitric oxide synthase 2 (Nos2), prostaglandin-endoperoxide synthase 2 (Ptgs2), and cyclin D1(Ccnd1) in colon tissue. These findings suggest that than compared with other cereal grain preparations, MCG-PC had a greater activity against AOM/DSS-induced CRC by reducing intestinal inflammation, and modulating the expression of certain carcinogenesis related factors (Nos2, Ptgs2, Tp53, Cdkn1a, Ccnd1 and Casp3) in colon tissue of CRC mice.

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“…A total of 12 patients (men from 70 to 88 years old), who underwent CRC resection at Limoges University Hospital (France) between March 2011 and April 2014, were enrolled in this retrospective study, according to the Declaration of Helsinki. Exclusion criteria were applied as described before . Tissue collection was approved by the local ethics committee (‘Comité de Protection des Personnes, Sud Ouest Outre Mer’; CPP SOOM4; number DC‐2008‐604).…”

Section: Methodsmentioning

confidence: 99%

Dual inhibition of BDNF/TrkB and autophagy: a promising therapeutic approach for colorectal cancer

Mazouffre

Geyl

Perraud

et al. 2017

J Cellular Molecular Medi

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Colorectal cancer (CRC) is the most common digestive cancer in the Western world. Despite effective therapies, resistance and/or recurrence frequently occur. The present study investigated the impact of two survival pathways-neurotrophic factors (TrkB/BDNF) and autophagy-on cell fate and tumour evolution. In vitro studies were performed on two CRC cell lines, SW480 (primary tumour) and SW620 (lymph node invasion), which were also used for subcutaneous xenografts on a nude mouse model. In addition, the presence of neurotrophic factors (NTs) and autophagy markers were assessed in tissue samples representative of different stages. On the basis of our previous study (which demonstrated that TrkB overexpression is associated with prosurvival signaling in CRC cells), we pharmacologically inhibited NTs pathways with K252a. As expected, an inactivation of the PI3K/AKT pathway was observed and CRC cells initiated autophagy. Conversely, blocking the autophagic flux with chloroquine or with ATG5-siRNA overactivated TrkB/BDNF signaling. In vitro, dual inhibition improved the effectiveness of single treatment by significantly reducing metabolic activity and enhancing apoptotic cell death. These findings were accentuated in vivo, in which dual inhibition induced a spectacular reduction in tumour volume following long-term treatment (21 days for K252a and 12 days for CQ). Finally, significant amounts of phospho-TrkB and LC3II were found in the patients' tissues, highlighting their relevance in CRC tumour biology. Taken together, our results show that targeting NTs and autophagy pathways potentially constitutes a new therapeutic approach for CRC.

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Implications of cleaved caspase 3 and AIF expression in colorectal cancer based on patient age

Cited by 6 publications

References 15 publications

Qingjie Fuzheng Granules regulates cancer cell proliferation, apoptosis and tumor angiogenesis in colorectal cancer xenograft mice via Sonic Hedgehog pathway

Qingjie Fuzheng Granules regulates cancer cell proliferation, apoptosis and tumor angiogenesis in colorectal cancer xenograft mice via Sonic Hedgehog pathway

Dietary Mixed Cereal Grains Ameliorate the Azoxymethane and Dextran Sodium Sulfate-Induced Colonic Carcinogenesis in C57BL/6J Mice

Dual inhibition of BDNF/TrkB and autophagy: a promising therapeutic approach for colorectal cancer

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