ArticlePloS one2016
Blockade of Inhibitors of Apoptosis Proteins in Combination with Conventional Chemotherapy Leads to Synergistic Antitumor Activity in Medulloblastoma and Cancer Stem-Like Cells.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 26 citations in OpenAlex.
- IAP antagonists induce anti-tumor immunity in multiple myeloma.Nature medicine · 2016Trial
- Redox-Regulated Pathways in Glioblastoma Stem-like Cells: Mechanistic Insights and Therapeutic Implications.Brain sciences · 2025Review
- Targeting the inhibitors of apoptosis proteins (IAPs) to combat drug resistance in cancers.Frontiers in pharmacology · 2025Review
- Neddylation of protein, a new strategy of protein post-translational modification for targeted treatment of central nervous system diseases.Frontiers in neuroscience · 2024Review
- Inhibiting the inhibitors: Development of the IAP inhibitor xevinapant for the treatment of locally advanced squamous cell carcinoma of the head and neck.Cancer treatment reviews · 2023Review
- Targeting the apoptosis pathway to treat tumours of the paediatric nervous system.Cell death & disease · 2022Review
- Drug and apoptosis resistance in cancer stem cells: a puzzle with many pieces.Cancer drug resistance (Alhambra, Calif.) · 2022Review
- Immunosuppression in Medulloblastoma: Insights into Cancer Immunity and Immunotherapy.Current treatment options in oncology · 2021Review
- Review
- Resistance to drugs and cell death in cancer stem cells (CSCs).Journal of translational science · 2020Article
- The effects of cucurbitacin E on GADD45β-trigger G2/M arrest and JNK-independent pathway in brain cancer cells.Journal of cellular and molecular medicine · 2019Article
- Butein induces apoptotic cell death of human cervical cancer cells.Oncology letters · 2018Article
- Targeting inhibitors of apoptosis proteins suppresses medulloblastoma cell proliferation via G2/M phase arrest and attenuated neddylation of p21.Cancer medicine · 2018Article
- Autophagic Mechanism in Anti-Cancer Immunity: Its Pros and Cons for Cancer Therapy.International journal of molecular sciences · 2017Review
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMedulloblastoma (MB) is the most common pediatric primary malignant brain tumor. Approximately one-third of MB patients succumb to treatment failure and some survivors suffer detrimental side effects. Hence, the purpose of this study is to explore new therapeutic regimens to overcome chemotherapeutic agent resistance or reduce chemotherapy-induced toxicity.
methodsWe detected the expression of inhibitors of apoptosis proteins (IAPs) in MB and CD133+ MB cell lines and MB tissues using immunoblotting and immunohistochemical staining. The antitumor effects of inhibitors against IAPs on MB or CD133+ MB cells were evaluated by MTT assay, Annexin V/PI analysis, and caspase-3/7 activity. Autophagy was assessed by the conversion of light chain (LC) 3-I to LC3-II and Cyto-ID autophagy detection kit.
resultsMB cells showed higher expression of IAPs compared to normal astrocytes and normal brain tissues. Conventional chemotherapeutic agents combined with small-molecule IAP inhibitors (LCL161 or LBW242) showed a synergistic effect in MB cells. Combined treatments triggered apoptosis in MB cells through activation of caspase-3/7 and autophagic flux simultaneously. In addition, we found that CD133+ MB cells with features of cancer stem cells displayed higher levels of X-linked inhibitor of apoptosis (XIAP) and cellular inhibitor of apoptosis 1/2 (cIAP1/2), and were hypersensitive to treatment with IAP inhibitors.
conclusionsThese results shed light on the biological effects of combination therapy on MB cells and illustrate that IAP inhibitors are more effective for CD133+ stem-like MB cells.
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