ArticleJournal of cellular and molecular medicine2014
The isothiocyanate erucin abrogates telomerase in hepatocellular carcinoma cells in vitro and in an orthotopic xenograft tumour model of HCC.
Article in Journal of cellular and molecular medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Τelomerase inhibitors and activators in aging and cancer: A systematic review.Molecular medicine reports · 2022Pooled it
- Short-Term Dietary Intervention with Cooked but Not RawNutrients · 2019Trial
- Article
- Small-molecule-based targeted therapy in liver cancer.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Review
- Chemopreventive aspects, investigational anticancer applications and current perspectives on allyl isothiocyanate (AITC): a review.Molecular and cellular biochemistry · 2023Review
- The Dietary Isothiocyanate Erucin Reduces Kidney Cell Motility by Disturbing Tubulin Polymerization.Molecular nutrition & food research · 2023Article
- Review
- Anticarcinogenic Effects of Isothiocyanates on Hepatocellular Carcinoma.International journal of molecular sciences · 2022Review
- Article
- Allyl Isothiocyanate: A TAS2R38 Receptor-Dependent Immune Modulator at the Interface Between Personalized Medicine and Nutrition.Frontiers in immunology · 2021Article
- Telomerase Inhibitors from Natural Products and Their Anticancer Potential.International journal of molecular sciences · 2017Review
- Sulforaphane exerts anti-angiogenesis effects against hepatocellular carcinoma through inhibition of STAT3/HIF-1α/VEGF signalling.Scientific reports · 2017Article
- The impact of cruciferous vegetable isothiocyanates on histone acetylation and histone phosphorylation in bladder cancer.Journal of proteomics · 2017Article
- Benzyl-isothiocyanate Induces Apoptosis and Inhibits Migration and Invasion of Hepatocellular Carcinoma CellsJournal of Cancer · 2017Article
- Allyl isothiocyanate induces replication-associated DNA damage response in NSCLC cells and sensitizes to ionizing radiation.Oncotarget · 2015Article
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In contrast to cancer cells, most normal human cells have no or low telomerase levels which makes it an attractive target for anti-cancer drugs. The small molecule sulforaphane from broccoli is known for its cancer therapeutic potential in vitro and in vivo. In animals and humans it was found to be quickly metabolized into 4-methylthiobutyl isothiocyanate (MTBITC, erucin) which we recently identified as strong selective apoptosis inducer in hepatocellular carcinoma (HCC) cells. Here, we investigated the relevance of telomerase abrogation for cytotoxic efficacy of MTBITC against HCC. The drug was effective against telomerase, independent from TP53 and MTBITC also blocked telomerase in chemoresistant subpopulations. By using an orthotopic human liver cancer xenograft model, we give first evidence that MTBITC at 50 mg/KG b.w./d significantly decreased telomerase activity in vivo without affecting enzyme activity of adjacent normal tissue. Upon drug exposure, telomerase decrease was consistent with a dose-dependent switch to anti-survival, cell arrest and apoptosis in our in vitro HCC models. Blocking telomerase by the specific inhibitor TMPyP4 further sensitized cancer cells to MTBITC-mediated cytotoxicity. Overexpression of hTERT, but not enzyme activity deficient DNhTERT, protected against apoptosis; neither DNA damage nor cytostasis induction by MTBITC was prevented by hTERT overexpression. These findings imply that telomerase enzyme activity does not protect against MTBITC-induced DNA damage but impacts signalling processes upstream of apoptosis execution level.
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