ArticlePloS one2011
BIM-mediated AKT phosphorylation is a key modulator of arsenic trioxide-induced apoptosis in cisplatin-sensitive and -resistant ovarian cancer cells.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 56 citations in OpenAlex.
- Disrupting Akt-Wnt/β-catenin signaling suppresses glioblastoma stem cell growth and tumor progression in immunocompetent mice.Journal of neuro-oncology · 2026Article
- Mechanisms of the JNK/p38 MAPK signaling pathway in drug resistance in ovarian cancer.Frontiers in oncology · 2025Review
- Arsenic-Induced Thyroid Hormonal Alterations and Their Putative Influence on Ovarian Follicles in Balb/c Mice.Biological trace element research · 2024Article
- Molecular pathways and therapeutic targets linked to triple-negative breast cancer (TNBC).Molecular and cellular biochemistry · 2024Review
- Metabolic pathways of potential miRNA biomarkers derived from liquid biopsy in epithelial ovarian cancer.Oncology letters · 2023Article
- Application of Arsenic Trioxide-Based Combined Sequential Chemotherapy in Recurrent Resistant and Refractory Ovarian Cancers: A Single-Center, Open Phase II Clinical Study.Journal of oncology · 2022Article
- Semi-Synthesis, Cytotoxic Evaluation, and Structure-Activity Relationships of Brefeldin A Derivatives with Antileukemia Activity.Marine drugs · 2021Article
- New Anti-Leukemic Effect of Carvacrol and Thymol Combination through Synergistic Induction of Different Cell Death Pathways.Molecules (Basel, Switzerland) · 2021Article
- Ceramide Regulates Anti-Tumor Mechanisms of Erianin in Androgen-Sensitive and Castration-Resistant Prostate Cancers.Frontiers in oncology · 2021Article
- Targeting folate receptor β positive tumor-associated macrophages in lung cancer with a folate-modified liposomal complex.Signal transduction and targeted therapy · 2020Article
- Beyond Cisplatin: Combination Therapy with Arsenic Trioxide.Inorganica chimica acta · 2019Article
- Arsenic compounds induce apoptosis through caspase pathway activation in MA-10 Leydig tumor cells.Oncology letters · 2019Article
- Article
- High BIM mRNA levels are associated with longer survival in advanced gastric cancer.Oncology letters · 2017Article
- Article
- 8‑bromo‑7‑methoxychrysin induces apoptosis by regulating Akt/FOXO3a pathway in cisplatin‑sensitive and resistant ovarian cancer cells.Molecular medicine reports · 2015Article
- Mitochondrial p53 phosphorylation induces Bak-mediated and caspase-independent cell death.Oncotarget · 2015Article
- Oncogenes associated with drug resistance in ovarian cancer.Journal of cancer research and clinical oncology · 2015Review
- A urokinase receptor-Bim signaling axis emerges during EGFR inhibitor resistance in mutant EGFR glioblastoma.Cancer research · 2015Article
- Caspase-9 mediates Puma activation in UCN-01-induced apoptosis.Cell death & disease · 2014Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundChemo-resistance to cisplatin-centered cancer therapy is a major obstacle to the effective treatment of human ovarian cancer. Previous reports indicated that arsenic trioxide (ATO) induces cell apoptosis in both drug-sensitive and -resistant ovarian cancer cells. PRINCIPAL
findingsIn this study, we determined the molecular mechanism of ATO-induced apoptosis in ovarian cancer cells. Our data demonstrated that ATO induced cell apoptosis by decreasing levels of phosphorylated AKT (p-AKT) and activating caspase-3 and caspase-9. Importantly, BIM played a critical role in ATO-induced apoptosis. The inhibition of BIM expression prevented AKT dephosphorylation and inhibited caspase-3 activation during cell apoptosis. However, surprisingly, gene silencing of AKT or FOXO3A had little effect on BIM expression and phosphorylation. Moreover, the activation of caspase-3 by ATO treatment improved AKT dephosphorylation, not only by cleaving the regulatory A subunit of protein phosphatase 2A (PP2A), but also by increasing its activation. Furthermore, our data indicated that the c-Jun N-terminal kinases (JNK) pathway is involved in the regulation of BIM expression.
conclusionsWe demonstrated the roles of BIM in ATO-induced apoptosis and the molecular mechanisms of BIM expression regulated by ATO during ovarian cancer cell apoptosis. Our findings suggest that BIM plays an important role in regulating p-AKT by activating caspase-3 and that BIM mediates the level of AKT phosphorylation to determine the threshold for overcoming cisplatin resistance in ovarian cancer cells.
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