ArticleWorld journal of gastroenterology2008
Bcl-x(L) and Myeloid cell leukaemia-1 contribute to apoptosis resistance of colorectal cancer cells.
Article in World journal of gastroenterology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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Who cites it
21 citing papers in PubMed, 42 citations in OpenAlex.
- Phase II trial of mapatumumab, a fully human agonistic monoclonal antibody that targets and activates the tumour necrosis factor apoptosis-inducing ligand receptor-1 (TRAIL-R1), in patients with refractory colorectal cancer.British journal of cancer · 2010Trial
- The Multifaceted Role of Annexin A1 in Colorectal Cancer: From Molecular Mechanisms to Predictive and Prognostic Implications.Medical sciences (Basel, Switzerland) · 2025Review
- Sodium Butyrate: A Multifaceted Modulator in Colorectal Cancer Therapy.Medicina (Kaunas, Lithuania) · 2025Article
- GSDMD-dependent pyroptotic induction by a multivalent CXCR4-targeted nanotoxin blocks colorectal cancer metastases.Drug delivery · 2022Article
- Dual Targeting of Anti-Apoptotic Proteins Enhances Chemosensitivity of the Acute Myeloid Leukemia Cells.Asian Pacific journal of cancer prevention : APJCP · 2022Article
- Scutellarin resensitizes oxaliplatin-resistant colorectal cancer cells to oxaliplatin treatment through inhibition of PKM2.Molecular therapy oncolytics · 2021Article
- Translationally controlled tumour protein TCTP is induced early in human colorectal tumours and contributes to the resistance of HCT116 colon cancer cells to 5-FU and oxaliplatin.Cell communication and signaling : CCS · 2017Article
- Obatoclax, a Pan-BCL-2 Inhibitor, Targets Cyclin D1 for Degradation to Induce Antiproliferation in Human Colorectal Carcinoma Cells.International journal of molecular sciences · 2016Article
- Article
- Bcl-xL promotes metastasis independent of its anti-apoptotic activity.Nature communications · 2016Article
- Inhibition of NANOG/NANOGP8 downregulates MCL-1 in colorectal cancer cells and enhances the therapeutic efficacy of BH3 mimetics.Clinical cancer research : an official journal of the American Association for Cancer Research · 2014Article
- Nanoencapsulation of ABT-737 and camptothecin enhances their clinical potential through synergistic antitumor effects and reduction of systemic toxicity.Cell death & disease · 2014Article
- Pan-Bcl-2 inhibitor obatoclax delays cell cycle progression and blocks migration of colorectal cancer cells.PloS one · 2014Article
- Beyond cell death - antiapoptotic Bcl-2 proteins regulate migration and invasion of colorectal cancer cells in vitro.PloS one · 2013Article
- The expression of Mcl-1 in human cervical cancer and its clinical significance.Medical oncology (Northwood, London, England) · 2012Article
- Race and subset analyses in clinical trials: time to get serious about data integration.Journal of the National Cancer Institute · 2011Article
- Wogonin and related natural flavones are inhibitors of CDK9 that induce apoptosis in cancer cells by transcriptional suppression of Mcl-1.Cell death & disease · 2011Article
- Article
- Cytomegalovirus and tumors: two players for one goal-immune escape.The open virology journal · 2011Article
- Correlation between Mcl-1 and pAKT protein expression in colorectal cancer.International journal of clinical and experimental pathology · 2010Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimTo explore the role of Bcl-x(L) and Myeloid cell leukaemia (Mcl)-1 for the apoptosis resistance of colorectal carcinoma (CRC) cells towards current treatment modalities.
methodsBcl-x(L) and Mcl-1 mRNA and protein expression were analyzed in CRC cell lines as well as human CRC tissue by Western blot, quantitative PCR and immunohistochemistry. Bcl-x(L) and Mcl-1 protein expression was knocked down or increased in CRC cell lines by applying specific siRNAs or expression plasmids, respectively. After modulation of protein expression, CRC cells were treated with chemotherapeutic agents, an antagonistic epidermal growth factor receptor (EGFR1) antibody, an EGFR1 tyrosine kinase inhibitor, or with the death receptor ligand TRAIL. Apoptosis induction and cell viability were analyzed.
resultsHere we show that in human CRC tissue and various CRC cell lines both Bcl-x(L) and Mcl-1 are expressed. Bcl-x(L) expression was higher in CRC tissue than in surrounding non-malignant tissue, both on protein and mRNA level. Mcl-1 mRNA expression was significantly lower in malignant tissues. However, protein expression was slightly higher. Viability rates of CRC cells were significantly decreased after knock down of Bcl-x(L) expression, and, to a lower extent, after knock down of Mcl-1 expression. Furthermore, cells with reduced Bcl-x(L) or Mcl-1 expression was more sensitive towards oxaliplatin- and irinotecan-induced apoptosis, and in the case of Bcl-x(L) also towards 5-FU-induced apoptosis. On the other hand, upregulation of Bcl-x(L) by transfection of an expression plasmid decreased chemotherapeutic drug-induced apoptosis. EGF treatment clearly induced Bcl-x(L) and Mcl-1 expression in CRC cells. Apoptosis induction upon EGFR1 blockage by cetuximab or PD168393 was increased by inhibiting Mcl-1 and Bcl-x(L) expression. More strikingly, CD95- and TRAIL-induced apoptosis was increased by Bcl-x(L) knock down.
conclusionOur data suggest that Bcl-x(L) and, to a lower extent, Mcl-1, are important anti-apoptotic factors in CRC. Specific downregulation of Bcl-x(L) is a promising approach to sensitize CRC cells towards chemotherapy and targeted therapy.
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