ArticleFrontiers in pharmacology2022
Pitavastatin Induces Cancer Cell Apoptosis by Blocking Autophagy Flux.
Article in Frontiers in pharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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10 citing papers in PubMed, 20 citations in OpenAlex.
- Advances regarding the mechanism of endoplasmic reticulum stress in diabetic kidney disease and pharmacological interventions (Review).Molecular medicine reports · 2026Review
- 27-Hydroxycholesterol in cancer development and drug resistance.Journal of enzyme inhibition and medicinal chemistry · 2025Review
- Pitavastatin is a novel Mcl-1 inhibitor that overcomes paclitaxel resistance in triple-negative breast cancer.Experimental hematology & oncology · 2025Article
- Cholesterol metabolism: molecular mechanisms, biological functions, diseases, and therapeutic targets.Molecular biomedicine · 2025Review
- Gene regulatory network topology governs resistance and treatment escape in glioma stem-like cells.Science advances · 2024Article
- Exploring a repurposed candidate with dual hIDO1/hTDO2 inhibitory potential for anticancer efficacy identified through pharmacophore-based virtual screening and in vitro evaluation.Scientific reports · 2024Article
- Role of protein degradation systems in colorectal cancer.Cell death discovery · 2024Review
- CD36 inhibition reduces non-small-cell lung cancer development through AKT-mTOR pathway.Cell biology and toxicology · 2024Article
- PD-1 signaling negatively regulates the common cytokine receptor γ chain via MARCH5-mediated ubiquitination and degradation to suppress anti-tumor immunity.Cell research · 2023Article
- Unraveling TIMP1: a multifaceted biomarker in colorectal cancer.Frontiers in genetics · 2023Article
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Authors and funding
4 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Statins, a class of lipid-lowering drugs, are used in drug repositioning for treatment of human cancer. However, the molecular mechanisms underlying statin-induced cancer cell death and autophagy are not clearly defined. In the present study, we showed that pitavastatin could increase apoptosis in a FOXO3a-dependent manner in the oral cancer cell line, SCC15, and the colon cancer cell line, SW480, along with the blockade of autophagy flux. The inhibition of autophagy by silencing the LC3B gene reduced apoptosis, while blockade of autophagy flux using its inhibitor, Bafilomycin A1, further induced apoptosis upon pitavastatin treatment, which suggested that autophagy flux blockage was the cause of apoptosis by pitavastatin. Further, the FOXO3a protein accumulated due to the blockade of autophagy flux which in turn was associated with the induction of ER stress by transcriptional upregulation of PERK-CHOP pathway, subsequently causing apoptosis due to pitavastatin treatment. Taken together, pitavastatin-mediated blockade of autophagy flux caused an accumulation of FOXO3a protein, thereby leading to the induction of PERK, ultimately causing CHOP-mediated apoptosis in cancer cells. Thus, the present study highlighted the additional molecular mechanism underlying the role of autophagy flux blockade in inducing ER stress, eventually leading to apoptosis by pitavastatin.
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