ArticlePloS one2009
RNA silencing of Mcl-1 enhances ABT-737-mediated apoptosis in melanoma: role for a caspase-8-dependent pathway.
Article in PloS one, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 78 citations in OpenAlex.
- The Role of Caspases in Melanoma Pathogenesis.Current issues in molecular biology · 2024Review
- Effective Targeting of Melanoma Cells by Combination of Mcl-1 and Bcl-2/Bcl-xInternational journal of molecular sciences · 2024Article
- Small molecules targeting protein-protein interactions for cancer therapy.Acta pharmaceutica Sinica. B · 2023Review
- Simultaneously Inhibiting BCL2 and MCL1 Is a Therapeutic Option for Patients with Advanced Melanoma.Cancers · 2020Article
- Inhibition of BCL2 Family Members Increases the Efficacy of Copper Chelation in BRAFCancer research · 2020Article
- Gene Therapy with MiRNA-Mediated Targeting of Mcl-1 Promotes the Sensitivity of Non-Small Cell Lung Cancer Cells to Treatment with ABT-737.Asian Pacific journal of cancer prevention : APJCP · 2020Article
- Focused screening reveals functional effects of microRNAs differentially expressed in colorectal cancer.BMC cancer · 2019Article
- Review
- BCL-XL and MCL-1 are the key BCL-2 family proteins in melanoma cell survival.Cell death & disease · 2019Article
- Immune surveillance in melanoma: From immune attack to melanoma escape and even counterattack.Cancer biology & therapy · 2017Review
- Combining a GSI and BCL-2 inhibitor to overcome melanoma's resistance to current treatments.Oncotarget · 2016Article
- Preferential targeting of cancer stem cells in the radiosensitizing effect of ABT-737 on HNSCC.Oncotarget · 2016Article
- CD19 chimeric antigen receptor (CD19 CAR)-redirected adoptive T-cell immunotherapy for the treatment of relapsed or refractory B-cell Non-Hodgkin's Lymphomas.American journal of cancer research · 2016Review
- Small molecule Mcl-1 inhibitors for the treatment of cancer.Pharmacology & therapeutics · 2015Review
- Antihelminthic benzimidazoles potentiate navitoclax (ABT-263) activity by inducing Noxa-dependent apoptosis in non-small cell lung cancer (NSCLC) cell lines.Cancer cell international · 2015Article
- Ionizing radiation sensitizes breast cancer cells to Bcl-2 inhibitor, ABT-737, through regulating Mcl-1.Radiation research · 2014Article
- Towards combinatorial targeted therapy in melanoma: from pre-clinical evidence to clinical application (review).International journal of oncology · 2014Review
- Regulation of Mcl-1 by constitutive activation of NF-κB contributes to cell viability in human esophageal squamous cell carcinoma cells.BMC cancer · 2014Article
- Targeted inhibition of FAK, PYK2 and BCL-XL synergistically enhances apoptosis in ovarian clear cell carcinoma cell lines.PloS one · 2014Article
- Silence of MCL-1 upstream signaling by shRNA abrogates multiple myeloma growth.Experimental hematology & oncology · 2014Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMalignant melanoma is resistant to almost all conventional forms of chemotherapy. Recent evidence suggests that anti-apoptotic proteins of the Bcl-2 family are overexpressed in melanoma and may contribute to melanoma's striking resistance to apoptosis. ABT-737, a small-molecule inhibitor of Bcl-2, Bcl-xl and Bcl-w, has demonstrated efficacy in several forms of leukemia, lymphoma as well as solid tumors. However, overexpression of Mcl-1, a frequent observance in melanoma, is known to confer ABT-737 resistance. METHODOLOGY/PRINCIPAL
findingsHere we report that knockdown of Mcl-1 greatly reduces cell viability in combination with ABT-737 in six different melanoma cell lines. We demonstrate that the cytotoxic effect of this combination treatment is due to apoptotic cell death involving not only caspase-9 activation but also activation of caspase-8, caspase-10 and Bid, which are normally associated with the extrinsic pathway of apoptosis. Caspase-8 (and caspase-10) activation is abrogated by inhibition of caspase-9 but not by inhibitors of the death receptor pathways. Furthermore, while caspase-8/-10 activity is required for the full induction of cell death with treatment, the death receptor pathways are not. Finally, we demonstrate that basal levels of caspase-8 and Bid correlate with treatment sensitivity. CONCLUSIONS/SIGNIFICANCE: Our findings suggest that the combination of ABT-737 and Mcl-1 knockdown represents a promising, new treatment strategy for malignant melanoma. We also report a death receptor-independent role for extrinsic pathway proteins in treatment response and suggest that caspase-8 and Bid may represent potential markers of treatment sensitivity.
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