ArticleClinical cancer research : an official journal of the American Association for Cancer Research2011
Pancreatic tumor suppression by benzyl isothiocyanate is associated with inhibition of PI3K/AKT/FOXO pathway.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It carries an expression of concern. Cited by 93 papers.
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Who cites it
93 citing papers in PubMed, 207 citations in OpenAlex.
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- Investigational Anticancer Potential and Targeted Delivery Aspects of Benzyl Isothiocyanate (BITC) in Breast Cancer Treatment.Applied biochemistry and biotechnology · 2026Review
- Functional Equivalence of Insulin and IGF-1 in the In Vitro Culture of Chicken Primordial Germ Cells.Genes · 2025Article
- Design and synthesis of 3,4-Frontiers in chemistry · 2025Article
- An extensive analysis of the prognostic and immune role of FOXO1 in various types of cancer.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2024Article
- CircHERC1 promotes non-small cell lung cancer cell progression by sequestering FOXO1 in the cytoplasm and regulating the miR-142-3p-HMGB1 axis.Molecular cancer · 2023Article
- Glucosinolates in cancer prevention and treatment: experimental and clinical evidence.Medical oncology (Northwood, London, England) · 2023Review
- LIPUS-SCs-Exo promotes peripheral nerve regeneration in cavernous nerve crush injury-induced ED rats via PI3K/Akt/FoxO signaling pathway.CNS neuroscience & therapeutics · 2023Article
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- Benzyl Isothiocyanate-Induced Cytotoxicity via the Inhibition of Autophagy and Lysosomal Function in AGS Cells.Biomolecules & therapeutics · 2022Article
- A novel panel of clinically relevant miRNAs signature accurately differentiates oral cancer from normal mucosa.Frontiers in oncology · 2022Article
- Cruciferous vegetables as a treasure of functional foods bioactive compounds: Targeting p53 family in gastrointestinal tract and associated cancers.Frontiers in nutrition · 2022Review
- New possible silver lining for pancreatic cancer therapy: Hydrogen sulfide and its donors.Acta pharmaceutica Sinica. B · 2021Review
- Role of Phytochemicals in Perturbation of Redox Homeostasis in Cancer.Antioxidants (Basel, Switzerland) · 2021Review
- FOXO1 Is a Critical Switch Molecule for Autophagy and Apoptosis of Sow Endometrial Epithelial Cells Caused by Oxidative Stress.Oxidative medicine and cellular longevity · 2021Article
- The biochemical and clinical implications of phosphatase and tensin homolog deleted on chromosome ten in different cancers.American journal of cancer research · 2021Review
33 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
- Expression of concern
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
purposeOur previous studies have shown that benzyl isothiocyanate (BITC) suppress pancreatic cancer growth by inducing apoptosis but the molecular mechanism was unclear. In this study we hypothesized the involvement of PI3K/AKT/FOXO pathway in BITC-induced apoptosis. EXPERIMENTAL
designMice were implanted BxPC-3 tumor xenografts and orally gavaged with 12 μmol BITC. Plasma and tumor BITC concentration was estimated by liquid chromatography/tandem mass spectrometry. BxPC-3 and PanC-1 cells were used to elucidate PI3K/AKT/FOXO pathway. Electrophoretic mobility shift assay (EMSA), DNA binding activity, immunofluorescence, and gene transfection were used to delineate the mechanism.
resultsBITC-treated mice showed 43% less tumor growth as compared with control mice and correlated well with the therapeutic concentrations of 6.5 μmol/L BITC achieved in plasma and 7.5 μmol/g BITC in tumor tissue. Western blot analyses and immunohistochemistry revealed that tumors from BITC-treated mice showed reduced phosphorylation of PI3K, AKT, PDK1, mTOR, FOXO1, and FOXO3a and increased apoptosis. Complementing our in vivo results, we made similar observations in a dose- and time-dependent manner in BITC-treated BxPC-3 and Panc-1 cells. Binding of FOXO1 with 14-3-3 proteins was also reduced drastically by BITC treatment indicating nuclear retention of FOXO1 and this observation was further confirmed with EMSA, immunofluorescence, DNA binding, and upregulation of FOXO-responsive proteins Bim, p27, and p21 in BxPC-3 cells. Overexpression of AKT by transient transfection significantly blocked the modulation of FOXO proteins and protected the cells from BITC-mediated apoptosis and growth suppression.
conclusionsOur results provide convincing evidence on the involvement of PI3K/AKT/FOXO pathway in BITC-mediated pancreatic tumor growth suppression.
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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.