ArticleExperimental & molecular medicine2010
Chlorpromazine activates p21Waf1/Cip1 gene transcription via early growth response-1 (Egr-1) in C6 glioma cells.
Article in Experimental & molecular medicine, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.
- Canonical and Non-Canonical Antipsychotics' Dopamine-Related Mechanisms of Present and Next Generation Molecules: A Systematic Review on Translational Highlights for Treatment Response and Treatment-Resistant Schizophrenia.International journal of molecular sciences · 2023Pooled it
- Repurposing chlorpromazine for the treatment of triple-negative breast cancer growth and metastasis based on modulation of mitochondria-mediated apoptosis and autophagy/mitophagy.British journal of cancer · 2025Article
- Novel Tetracyclic Azaphenothiazines with the Quinoline Ring as New Anticancer and Antibacterial Derivatives of Chlorpromazine.International journal of molecular sciences · 2024Article
- Targeting GRP75 with a Chlorpromazine Derivative Inhibits Endometrial Cancer Progression Through GRP75-IP3R-CaAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- A Surprising Repurposing of Central Nervous System Drugs against Squamous Cell Carcinoma of the Bladder, UM-UC-5.Pharmaceutics · 2024Article
- N6-methyladenosine reader YTHDF2 promotes multiple myeloma cell proliferation through EGR1/p21Oncogene · 2023Article
- The dark side of mRNA translation and the translation machinery in glioblastoma.Frontiers in cell and developmental biology · 2023Review
- Glioblastoma: Current Status, Emerging Targets, and Recent Advances.Journal of medicinal chemistry · 2022Review
- The Impact of the Antipsychotic Medication Chlorpromazine on Cytotoxicity through CaNeurotoxicity research · 2022Article
- Wnt and PI3K/Akt/mTOR Survival Pathways as Therapeutic Targets in Glioblastoma.International journal of molecular sciences · 2022Review
- Review
- Repurposing Antipsychotics for Cancer Treatment.Biomedicines · 2021Review
- Chlorpromazine induces cytotoxic autophagy in glioblastoma cells via endoplasmic reticulum stress and unfolded protein response.Journal of experimental & clinical cancer research : CR · 2021Article
- Multifaceted effect of chlorpromazine in cancer: implications for cancer treatment.Oncotarget · 2021Article
- Anticancer Properties of the Antipsychotic Drug Chlorpromazine and Its Synergism With Temozolomide in Restraining Human Glioblastoma ProliferationFrontiers in oncology · 2021Article
- Drug rechanneling: A novel paradigm for cancer treatment.Seminars in cancer biology · 2021Review
- ERα-related chromothripsis enhances concordant gene transcription on chromosome 17q11.1-q24.1 in luminal breast cancer.BMC medical genomics · 2020Article
- New drugs are not enough‑drug repositioning in oncology: An update.International journal of oncology · 2020Review
- CRISPR-dCas9-Based Artificial Transcription Factors to Improve Efficacy of Cancer Treatment With Drug Repurposing: Proposal for Future Research.Frontiers in oncology · 2020Review
- Refocusing the Use of Psychiatric Drugs for Treatment of Gastrointestinal Cancers.Frontiers in oncology · 2020Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
2-Chloro-10-[3(-dimethylamino)propyl]phenothiazinemonohydrochloride (chlorpromazine) is a phenothiazine derivative used clinically to control psychotic disorders. It also exhibits an anticancer activity. Treatment with chlorpromazine (CPZ) results in cell-cycle arrest at the G2/M phase in rat C6 glioma cells. CPZ reduces the expression of cell cycle-related proteins, such as cyclin D1, cyclin A, and cyclin B1, but causes an increase in the p21(Waf1/Cip1) level. The molecular mechanism by which CPZ regulates p21(Waf1/Cip1) expression is unknown. Here, we provide evidence that CPZ activates the p21(Waf1/Cip1) gene promoter via induction of the transcription factor early growth response-1 (Egr-1) independently of p53 in C6 cells. A point mutation in the Egr-1-binding motif within the p21(Waf1/Cip1) promoter abrogated promoter inducibility due to CPZ. Forced expression of Egr-1 enhanced p21(Waf1/Cip1) promoter activity. In contrast, knockdown of endogenous Egr-1 by small interference RNA attenuated CPZ-induced p21(Waf1/Cip1) promoter activity. A chromatin immunoprecipitation assay demonstrated that Egr-1 binds to the p21(Waf1/Cip1) gene promoter. Further analysis showed that the ERK and JNK MAP kinases are required for induction of Egr-1 by CPZ. Finally, stable silencing of Egr-1 expression lead to attenuated CPZ-inducible p21(Waf1/Cip1) expression and inhibited G2/M phase cell-cycle arrest. These results demonstrate that a functional link between ERK and JNK MAP kinase pathways and p21(Waf1/Cip1) induction via Egr-1 contributes to CPZ-induced anticancer activity in C6 glioma cells.
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Registered trials
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