Journal article
Sulforaphane induces autophagy by inhibition of HDAC6-mediated PTEN activation in triple negative breast cancer cells
Life sciences (1973), Vol.213, pp.149-157
11/15/2018
DOI: 10.1016/j.lfs.2018.10.034
PMID: 30352240
Abstract
To study the underlying mechanisms of sulforaphane, a natural histone deacetylase (HDAC) inhibitor, in inhibiting triple negative breast cancer cells growth and the therapeutic effects of combination of sulforaphane and doxorubicin in TNBC treatment.
The antineoplastic activity of sulforaphane was evaluated in MDA-MB-231, BT549 and MDA-MB-468 cells with MTT assay. Cell apoptosis was detected with Annexin V/PI double staining by Flow cytometry. Cell autophagy was detected with fluorescence microscope. The effects of Sulforaphane and Doxorubicin combination treatments on cells growth were determined with Chou-Talalay median effect/combination index (CI) model. mRNA and protein expression of genes were assayed respectively with real-time PCR and Western bloting. Protein-protein interaction was detected with co-immunoprecipation. Gene knock-down was performed with small interfere RNA. In vivo assay of combinational treatment with sulforaphane and doxorubicin was investigated in athymic nude mice bearing MDA-MB-231 xenografts.
Results showed that sulforaphane inhibited cell growth and induced autophagy in MDA-MB-231, BT549 and MDA-MB-468 cells. Further study demonstrated that sulforaphane induced autophagy by down-regulating expression of HDAC6, which resulted in increased membrane translocation and acetylation modification of phosphatase and tensin homolog (PTEN). Sulforaphane and doxorubicin combination exhibited a synergistic inhibition on TNBC cells growth. In nude mice, the combination of sulforaphane and doxorubicin displayed a greater inhibitory effect on MDA-MB-231 xenografts growth as compared to either treatment alone.
Our study suggested that induction of autophagy by targeting HDAC6 in combination with chemotherapeutic reagent may provide a novel strategy for TNBC therapy.
[Display omitted]
Details
- Title: Subtitle
- Sulforaphane induces autophagy by inhibition of HDAC6-mediated PTEN activation in triple negative breast cancer cells
- Creators
- Fan Yang - China Three Gorges UniversityFaling Wang - China Three Gorges UniversityYuni Liu - China Three Gorges UniversityShien Wang - China Three Gorges UniversityXin Li - China Three Gorges UniversityYi Huang - UPMC Hillman Cancer CenterYan Xia - Hubei University for NationalitiesChunyu Cao - China Three Gorges University
- Resource Type
- Journal article
- Publication Details
- Life sciences (1973), Vol.213, pp.149-157
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.lfs.2018.10.034
- PMID
- 30352240
- ISSN
- 0024-3205
- eISSN
- 1879-0631
- Grant note
- DOI: 10.13039/501100001809, name: National Natural Science Foundation of China, award: 81772833; DOI: 10.13039/501100003819, name: Natural Science Foundation of Hubei province, award: 2017CFB556; name: Scientific research and developing project of Yichang, award: A17-301-23; name: Open Foundation of Key Laboratory of Occurrence and Intervention of Rheumatic Diseases of Hubei Province, award: OIR13012A, OIR13003A
- Language
- English
- Date published
- 11/15/2018
- Academic Unit
- Internal Medicine
- Record Identifier
- 9984383282002771
Metrics
2 Record Views