ArticleJournal of cellular and molecular medicine2015
HDAC-inhibitor (S)-8 disrupts HDAC6-PP1 complex prompting A375 melanoma cell growth arrest and apoptosis.
Article in Journal of cellular and molecular medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 20 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- RETRACTION: HDAC-Inhibitor (S)-8 Disrupts HDAC6-PP1 Complex Prompting A375 Melanoma Cell Growth Arrest and Apoptosis.Journal of cellular and molecular medicine · 2026Article
- Lactic acid inhibits melanin synthesis by regulating histone H3 lactylation and suppressing tyrp1 transcription in B16 melanoma cells.Scientific reports · 2025Article
- WT161, a selective HDAC6 inhibitor, decreases growth, enhances chemosensitivity, promotes apoptosis, and suppresses motility of melanoma cells.Cancer chemotherapy and pharmacology · 2025Article
- Histones deacetylases in the epidermis: structure, functions and therapeutic implications.Frontiers in epigenetics and epigenomics · 2025Review
- Targeting histone deacetylase suppresses tumor growth through eliciting METTL14-modified mCancer communications (London, England) · 2023Article
- The roles of histone modifications in tumorigenesis and associated inhibitors in cancer therapy.Journal of the National Cancer Center · 2022Review
- The Role of HDACs in the Response of Cancer Cells to Cellular Stress and the Potential for Therapeutic Intervention.International journal of molecular sciences · 2022Review
- Histone Deacetylase (HDAC) Inhibitors: A Promising Weapon to Tackle Therapy Resistance in Melanoma.International journal of molecular sciences · 2022Review
- Chidamide Reverses Fluzoparib Resistance in Triple-Negative Breast Cancer Cells.Frontiers in oncology · 2022Article
- Article
- 2-Methylquinazoline derivative 23BB as a highly selective histone deacetylase 6 inhibitor alleviated cisplatin-induced acute kidney injury.Bioscience reports · 2020Article
- Off-target toxicity is a common mechanism of action of cancer drugs undergoing clinical trials.Science translational medicine · 2019Article
- DNA Methyltransferase Inhibitors: Catalysts For Antitumour Immune Responses.OncoTargets and therapy · 2019Review
- Histone deacetylase 6 in cancer.Journal of hematology & oncology · 2018Review
- Histone Deacetylase Inhibitors as Anticancer Drugs.International journal of molecular sciences · 2017Review
- Inhibition of polypyrimidine tract-binding protein 3 induces apoptosis and cell cycle arrest, and enhances the cytotoxicity of 5- fluorouracil in gastric cancer cells.British journal of cancer · 2017Article
- The histone deacetylase inhibitor trichostatin a decreases lymphangiogenesis by inducing apoptosis and cell cycle arrest via p21-dependent pathways.BMC cancer · 2016Article
- Changes in 30K protein synthesis during delayed degeneration of the silk gland by a caspase-dependent pathway in a Bombyx (silkworm) mutant.Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology · 2016Article
- HDAC1 controls CIP2A transcription in human colorectal cancer cells.Oncotarget · 2016Article
- HDAC Inhibitors as Epigenetic Regulators of the Immune System: Impacts on Cancer Therapy and Inflammatory Diseases.BioMed research international · 2016Review
Corrections and comments
- Retraction · 2026-01-29Duplication of/in Image · Investigation by Journal/Publisher · Investigation by Third Party · Objections by Author(s) · Unreliable Results and/or Conclusions ·
- Retracted
Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Histone deacetylase inhibitors (HDACi) are agents capable of inducing growth arrest and apoptosis in different tumour cell types. Previously, we reported a series of novel HDACi obtained by hybridizing SAHA or oxamflatin with 1,4-benzodiazepines. Some of these hybrids proved effective against haematological and solid cancer cells and, above all, compound (S)-8 has emerged for its activities in various biological systems. Here, we describe the effectiveness of (S)-8 against highly metastatic human A375 melanoma cells by using normal PIG1 melanocytes as control. (S)-8 prompted: acetylation of histones H3/H4 and α-tubulin; G0 /G1 and G2 /M cell cycle arrest by rising p21 and hypophos-phorylated RB levels; apoptosis involving the cleavage of PARP and caspase 9, BAD protein augmentation and cytochrome c release; decrease in cell motility, invasiveness and pro-angiogenic potential as shown by results of wound-healing assay, down-regulation of MMP-2 and VEGF-A/VEGF-R2, besides TIMP-1/TIMP-2 up-regulation; and also intracellular accumulation of melanin and neutral lipids. The pan-caspase inhibitor Z-VAD-fmk, but not the antioxidant N-acetyl-cysteine, contrasted these events. Mechanistically, (S)-8 allows the disruption of cytoplasmic HDAC6-protein phosphatase 1 (PP1) complex in A375 cells thus releasing the active PP1 that dephosphorylates AKT and blocks its downstream pro-survival signalling. This view is consistent with results obtained by: inhibiting PP1 with Calyculin A; using PPP1R2-transfected cells with impaired PP1 activity; monitoring drug-induced HDAC6-PP1 complex re-shuffling; and, abrogating HDAC6 expression with specific siRNA. Altogether, (S)-8 proved very effective against melanoma A375 cells, but not normal melanocytes, and safe to normal mice thus offering attractive clinical prospects for treating this aggressive malignancy.
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