ArticleCell death & disease2021
Sulforaphane downregulated fatty acid synthase and inhibited microtubule-mediated mitophagy leading to apoptosis.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 40 citations in OpenAlex.
- Lipid Metabolic Reprogramming in Lung Cancer: Mechanisms and Therapeutic Targets in the Tumor Microenvironment.International journal of cancer · 2026Review
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- Isothiocyanates in Cancer Therapeutics - A Molecular Perspective.Chemistry & biodiversity · 2026Review
- Sulforaphane Synergies with Phytochemicals and Pharmaceuticals: Implications for Healthspan.Medicines (Basel, Switzerland) · 2026Review
- Sulforaphane in Cancer Prevention and Therapy: A State-of-the-Art Review of Epidemiological Evidence, Molecular Mechanisms, and Translational Challenges.International journal of molecular sciences · 2026Review
- Dual Roles of NIX/BNIP3L in Tumors: Friend or Foe.Biology · 2026Review
- Sulforaphane as a Multi-Scale Mechano-Modulator in Cancer: An Integrative Perspective.Biology · 2026Article
- TFAP2A induces cisplatin resistance via BNIP3-mediated mitophagy in non-small cell lung cancer.Translational cancer research · 2025Article
- A Covalent and Modulable Inhibitor of the Tubulin-Microtubule System: Insights Into the Mechanism of Cacalol.Chemical biology & drug design · 2025Article
- Targeting mitochondria and programmed cell death as potential interventions for metastatic castration-resistant prostate cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Review
- TUBB4A Inhibits Glioma Development by Regulating ROS-PINK1/Parkin-Mitophagy Pathway.Molecular neurobiology · 2025Article
- Fatty acid synthase inhibition alleviates lung fibrosis via β-catenin signal in fibroblasts.Life science alliance · 2025Article
- Comprehensive RNA-seq analysis of benign prostatic hyperplasia (BPH) in rats exposed to testosterone and estradiol.Scientific reports · 2025Article
- Fatty acid metabolism in gouty arthritis: mechanisms to therapeutic targeting.Frontiers in immunology · 2025Review
- Plant-Derived Anti-Cancer Therapeutics and Biopharmaceuticals.Bioengineering (Basel, Switzerland) · 2024Review
- The roles and mechanisms of SREBP1 in cancer development and drug response.Genes & diseases · 2024Review
- Roles of Phytochemicals in Cancer Prevention and Therapeutics.International journal of molecular sciences · 2024Article
- Dietary isothiocyanates and anticancer agents: exploring synergism for improved cancer management.Frontiers in nutrition · 2024Review
- NTRK1 knockdown induces mouse cognitive impairment and hippocampal neuronal damage through mitophagy suppression via inactivating the AMPK/ULK1/FUNDC1 pathway.Cell death discovery · 2023Article
- Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
We previously demonstrated that sulforaphane (SFN) inhibited autophagy leading to apoptosis in human non-small cell lung cancer (NSCLC) cells, but the underlying subcellular mechanisms were unknown. Hereby, high-performance liquid chromatography-tandem mass spectrometry uncovered that SFN regulated the production of lipoproteins, and microtubule- and autophagy-associated proteins. Further, highly expressed fatty acid synthase (FASN) contributed to cancer malignancy and poor prognosis. Results showed that SFN depolymerized microtubules, downregulated FASN, and decreased its binding to α-tubulin; SFN downregulated FASN, acetyl CoA carboxylase (ACACA), and ATP citrate lyase (ACLY) via activating proteasomes and downregulating transcriptional factor SREBP1; SFN inhibited the interactions among α-tubulin and FASN, ACACA, and ACLY; SFN decreased the amount of intracellular fatty acid (FA) and mitochondrial phospholipids; and knockdown of FASN decreased mitochondrial membrane potential (ΔΨm) and increased reactive oxygen species, mitochondrial abnormality, and apoptosis. Further, SFN downregulated mitophagy-associated proteins Bnip3 and NIX, and upregulated mitochondrial LC3 II/I. Transmission electron microscopy showed mitochondrial abnormality and accumulation of mitophagosomes in response to SFN. Combined with mitophagy inducer CCCP or autophagosome-lysosome fusion inhibitor Bafilomycin A1, we found that SFN inhibited mitophagosome-lysosome fusion leading to mitophagosome accumulation. SFN reduced the interaction between NIX and LC3 II/I, and reversed CCCP-caused FA increase. Furthermore, knockdown of α-tubulin downregulated NIX and BNIP3 production, and upregulated LC3 II/I. Besides, SFN reduced the interaction and colocalization between α-tubulin and NIX. Thus, SFN might cause apoptosis via inhibiting microtubule-mediated mitophagy. These results might give us a new insight into the mechanisms of SFN-caused apoptosis in the subcellular level.
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Registered trials
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.