ArticleDrug design, development and therapy2015
The investigational Aurora kinase A inhibitor alisertib (MLN8237) induces cell cycle G2/M arrest, apoptosis, and autophagy via p38 MAPK and Akt/mTOR signaling pathways in human breast cancer cells.
Article in Drug design, development and therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 101 citations in OpenAlex.
- Randomized Phase III Study of Alisertib or Investigator's Choice (Selected Single Agent) in Patients With Relapsed or Refractory Peripheral T-Cell Lymphoma.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2019Trial
- Therapy-induced senescence rewires the melanoma secretome to promote antitumor immune response and augment cell therapies.Journal for immunotherapy of cancer · 2026Article
- AURKA/PHB2 signaling drives acquired resistance to KRASCell death discovery · 2026Article
- AURKA modulates tight junction functionality to influence the proliferation and metastasis of lung adenocarcinoma.Molecular and cellular biochemistry · 2026Article
- Article
- Combination therapy with alisertib enhances the anti-tumor immunity induced by a liver cancer vaccine.iScience · 2025Article
- Interplay of aurora kinase a functional residues and Epstein-barr Nuclear Antigen 1 in Epstein-barr virus associated Gastric cancer using AGS cells.BMC cancer · 2025Article
- Targeted Management: Unlocking the Crucial Role of PROTACs in Cancer Treatment.Current drug discovery technologies · 2025Review
- Physicochemistry, Nutritional, and Therapeutic Potential ofDrug design, development and therapy · 2024Review
- Transcriptomics analyses reveal the effects of Pentagamaboronon-0-ol on PI3K/Akt and cell cycle of HER2+ breast cancer cells.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2023Article
- CK1 Is a Druggable Regulator of Microtubule Dynamics and Microtubule-Associated Processes.Cancers · 2022Review
- New Advances in Targeted Therapy of HER2-Negative Breast Cancer.Frontiers in oncology · 2022Review
- Marchantia polymorpha L. ethanol extract induces apoptosis in hepatocellular carcinoma cells via intrinsic- and endoplasmic reticulum stress-associated pathways.Chinese medicine · 2021Article
- Identification and characterization of deschloro-chlorothricin obtained from a large natural product library targeting aurora A kinase in multiple myeloma.Investigational new drugs · 2021Article
- Differential reprogramming of breast cancer subtypes in 3D cultures and implications for sensitivity to targeted therapy.Scientific reports · 2021Article
- Mitotic Poisons in Research and Medicine.Molecules (Basel, Switzerland) · 2020Review
- Deoxypodophyllotoxin, a Lignan fromInternational journal of molecular sciences · 2020Article
- How Different Are the Molecular Mechanisms of Nodal and Distant Metastasis in Luminal A Breast Cancer?Cancers · 2020Article
- Preclinical and Dose-Finding Phase I Trial Results of Combined Treatment with a TORC1/2 Inhibitor (TAK-228) and Aurora A Kinase Inhibitor (Alisertib) in Solid Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Article
- Sauchinone: a prospective therapeutic agent-mediated EIF4EBP1 down-regulation suppresses proliferation, invasion and migration of lung adenocarcinoma cells.Journal of natural medicines · 2020Article
Corrections and comments
- Retracted
Authors and funding
11 authors at 8 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alisertib (ALS) is an investigational potent Aurora A kinase inhibitor currently undergoing clinical trials for the treatment of hematological and non-hematological malignancies. However, its antitumor activity has not been tested in human breast cancer. This study aimed to investigate the effect of ALS on the growth, apoptosis, and autophagy, and the underlying mechanisms in human breast cancer MCF7 and MDA-MB-231 cells. In the current study, we identified that ALS had potent growth-inhibitory, pro-apoptotic, and pro-autophagic effects in MCF7 and MDA-MB-231 cells. ALS arrested the cells in G2/M phase in MCF7 and MDA-MB-231 cells which was accompanied by the downregulation of cyclin-dependent kinase (CDK)1/cell division cycle (CDC) 2, CDK2, and cyclin B1 and upregulation of p21 Waf1/Cip1, p27 Kip1, and p53, suggesting that ALS induces G2/M arrest through modulation of p53/p21/CDC2/cyclin B1 pathways. ALS induced mitochondria-mediated apoptosis in MCF7 and MDA-MB-231 cells; ALS significantly decreased the expression of B-cell lymphoma 2 (Bcl-2), but increased the expression of B-cell lymphoma 2-associated X protein (Bax) and p53-upregulated modulator of apoptosis (PUMA), and increased the expression of cleaved caspases 3 and 9. ALS significantly increased the expression level of membrane-bound microtubule-associated protein 1 light chain 3 (LC3)-II and beclin 1 and induced inhibition of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) and p38 mitogen-activated protein kinase (MAPK) pathways in MCF7 and MDA-MB-231 cells as indicated by their altered phosphorylation, contributing to the pro-autophagic activities of ALS. Furthermore, treatment with wortmannin markedly downregulated ALS-induced p38 MAPK activation and LC3 conversion. In addition, knockdown of the p38 MAPK gene by ribonucleic acid interference upregulated Akt activation and resulted in LC3-II accumulation. These findings indicate that ALS promotes cellular apoptosis and autophagy in breast cancer cells via modulation of p38 MAPK/Akt/mTOR pathways. Further studies are warranted to further explore the molecular targets of ALS in the treatment of breast cancer.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.