Title:YF343, A Novel Histone Deacetylase Inhibitor, Combined with CQ
to Inhibit- Autophagy, Contributes to Increased Apoptosis in Triple-
Negative Breast Cancer
Volume: 30
Issue: 40
关键词:
HDACi，三阴性乳腺癌，细胞凋亡，自噬，氯喹，E2F7。
摘要:
Background: Compounds that target tumor epigenetic events are likely to constitute
a prominent strategy for anticancer treatment. Histone deacetylase inhibitors (HDACis)
have been developed as prospective candidates in anticancer drug development,
and currently, many of them are under clinical investigation. We assessed the anticancer
efficacy of a now hydroxamate-based HDACi, YF-343, in triple-negative breast cancer
development and studied its potential mechanisms.
Methods: YF-343 was estimated as a novel HDACi by the HDACi drug screening kit.
The biological effects of YF-343 in a panel of breast cancer cell lines were analyzed by
Western blot and flow cytometry. YF-343 exhibited notable cytotoxicity, promoted apoptosis,
and induced cell cycle arrest. Furthermore, it also induced autophagy, which plays
a pro-survival role in breast cancer cells.
Results: The combination of YF-343 with an autophagy inhibitor chloroquine (CQ) significantly
suppressed breast tumor progression as compared to the YF-343 treatment alone
both in vitro and in vivo. Mechanistically, the molecular mechanism of YF-343 on autophagy
was elucidated by gene chip expression profiles, qPCR analysis, luciferase reporter
gene assay, chromatin immunoprecipitation assays, immunohistochemical analysis,
and other methods. E2F7, a transcription factor, promoted the expression of ATG2A
via binding to the ATG2A promoter region and then induced autophagy in triple-negative
breast cancer cells treated with YF-343.
Conclusion: Our studies have illustrated the mechanisms for potential action of YF-343
on tumor growth in breast cancer models with pro-survival autophagy. The combination
therapy of YF-343 and CQ maybe a promising strategy for breast cancer therapy.
