ArticleApoptosis : an international journal on programmed cell death2012
Targeting colorectal cancer stem cells with inducible caspase-9.
Article in Apoptosis : an international journal on programmed cell death, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 48 citations in OpenAlex.
- Next-generation CAR-T and CAR-NK cell therapies in hematologic malignancies: engineering for persistence, specificity, and safety.Discover oncology · 2026Review
- The concealed side of caspases: beyond a killer of cells.Cellular and molecular life sciences : CMLS · 2024Review
- Identification of pyroptosis-related signature and development of a novel prognostic model in diffuse large B-cell lymphoma.Journal of cancer research and clinical oncology · 2023Article
- EMP1Cell research · 2023Article
- Caspase-9 driven murine model of selective cell apoptosis and efferocytosis.Cell death & disease · 2023Article
- Cell-to-cell variability in inducible Caspase9-mediated cell death.Cell death & disease · 2022Article
- Inclusion of the Inducible Caspase 9 Suicide Gene in CAR Construct Increases Safety of CAR.CD19 T Cell Therapy in B-Cell Malignancies.Frontiers in immunology · 2021Article
- Identification of the Pyroptosis-Related Gene Signature and Risk Score Model for Colon Adenocarcinoma.Frontiers in genetics · 2021Article
- Targeted Integration of Inducible Caspase-9 in Human iPSCs Allows EfficientInternational journal of molecular sciences · 2020Article
- FKBP Ligands-Where We Are and Where to Go?Frontiers in pharmacology · 2018Review
- Visualization and targeting of LGR5Nature · 2017Article
- Clinicopathologic Significance of Survivin Expression in Relation to CD133 Expression in Surgically Resected Stage II or III Colorectal Cancer.Journal of pathology and translational medicine · 2017Article
- Cancer Stem Cell and Gastrointestinal Cancer: Current Status, Targeted Therapy and Future Implications.Biochemistry & pharmacology : open access · 2016Article
- Decreased mitochondrial priming determines chemoresistance of colon cancer stem cells.Cell death and differentiation · 2014Article
- Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Colorectal cancer stem cells (CSCs) drive tumor growth and are suggested to initiate distant metastases. Moreover, colon CSCs are reportedly more resistant to conventional chemotherapy, which is in part due to upregulation of anti-apoptotic Bcl-2 family members. To determine whether we could circumvent this apoptotic blockade, we made use of an inducible active caspase-9 (iCasp9) construct to target CSCs. Dimerization of iCasp9 with AP20187 in HCT116 colorectal cancer cells resulted in massive and rapid induction of apoptosis. In contrast to fluorouracil (5-FU)-induced apoptosis, iCasp9-induced apoptosis was independent of the mitochondrial pathway as evidenced by Bax/Bak double deficient HCT116 cells. Dimerizer treatment of colon CSCs transduced with iCasp9 (CSC-iCasp9) also rapidly induced high levels of apoptosis, while these cells were unresponsive to 5-FU in vitro. More importantly, injection of the dimerizer into mice that developed a colon CSC-iCasp9-induced tumor resulted in a strong decrease in tumor size, an increase in tumor cell apoptosis and a clear loss of CD133(+) CSCs. Taken together, our data indicate that dimerization of iCasp9 circumvents the apoptosis block in CSCs, which results in effective tumor regression in vivo.
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