ArticleScientific reports2018
Induction of N-Ras degradation by flunarizine-mediated autophagy.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 21 citations in OpenAlex.
- Review
- Elevated NRAS expression during DCIS is a potential driver for progression to basal-like properties and local invasiveness.Breast cancer research : BCR · 2022Article
- Preclinical Development of Seriniquinones as Selective Dermcidin Modulators for the Treatment of Melanoma.Marine drugs · 2022Review
- Seriniquinones as Therapeutic Leads for Treatment of BRAF and NRAS Mutant Melanomas.Molecules (Basel, Switzerland) · 2021Article
- Allicin induces cell cycle arrest and apoptosis of breast cancer cells in vitro via modulating the p53 pathway.Molecular biology reports · 2021Article
- Small Molecules Targeting Programmed Cell Death in Breast Cancer Cells.International journal of molecular sciences · 2021Review
- A chemical genomics-aggrephagy integrated method studying functional analysis of autophagy inducers.Autophagy · 2021Article
- Drug repurposing for breast cancer therapy: Old weapon for new battle.Seminars in cancer biology · 2021Review
- Multi-Targeted Anticancer Activity of Imidazolate Phosphane Gold(I) Compounds by Inhibition of DHFR and TrxR in Breast Cancer Cells.Frontiers in chemistry · 2020Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
Abstract
Ras GTPases are powerful drivers for tumorigenesis, but directly targeting Ras for treating cancer remains challenging. The growth and transforming activity of the aggressive basal-like breast cancer (BLBC) are driven by N-Ras. To target N-Ras in BLBC, this study screened existing pharmacologically active compounds for the new ability to induce N-Ras degradation, which led to the identification of flunarizine (FLN), previously approved for treating migraine and epilepsy. The FLN-induced N-Ras degradation was not affected by a 26S-proteasome inhibitor. Rather, it was blocked by autophagy inhibitors. Furthermore, N-Ras can be seen co-localized with active autophagosomes upon FLN treatment, suggesting that FLN alters the autophagy pathway to degrade N-Ras. Importantly, FLN treatment recapitulated the effect of N-RAS silencing in vitro by selectively inhibiting the growth of BLBC cells, but not that of breast cancer cells of other subtypes. In addition, in vivo FLN inhibited tumor growth of a BLBC xenograft model. In conclusion, this proof-of-principle study presents evidence that the autophagy pathway can be coerced by small molecule inhibitors, such as FLN, to degrade Ras as a strategy to treat cancer. FLN has low toxicity and should be further investigated to enrich the toolbox of cancer therapeutics.
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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.