期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 20, 期 4, 页码 -出版社
MDPI
DOI: 10.3390/ijms20040804
关键词
histone deacetylase inhibitor; breast cancer cells; cell viability; cell cycle; apoptosis; autophagy; reactive oxygen species; mitochondrial transmembrane potential
资金
- University of Palermo (Italy) [FFR 2018]
- Royal Thai Government
- EPSRC [EP/P026990/1]
- EPSRC [EP/I037229/1, EP/P026990/1] Funding Source: UKRI
We examined the effects of the ferrocene-based histone deacetylase-3 inhibitor Pojamide (N-1-(2-aminophenyl)-N-8-ferrocenyloctanediamide) and its two derivatives N-1-(2-aminophenyl)-N-6-ferrocenyladipamide and N-1-(2-aminophenyl)-N-8-ferroceniumoctanediamide tetrafluoroborate on triple-negative MDA-MB-231 breast cancer cells. Viability/growth assays indicated that only the first two compounds at 70 M concentration caused an approximate halving of cell number after 24 h of exposure, whereas the tetrafluoroborate derivative exerted no effect on cell survival nor proliferation. Flow cytometric and protein blot analyses were performed on cells exposed to both Pojamide and the ferrocenyladipamide derivative to evaluate cell cycle distribution, apoptosis/autophagy modulation, and mitochondrial metabolic state in order to assess the cellular basis of the cytotoxic effect. The data obtained show that the cytotoxic effect of the two deacetylase inhibitors may be ascribed to the onset of non-apoptotic cell death conceivably linked to a down-regulation of autophagic processes and an impairment of mitochondrial function with an increase in intracellular reactive oxygen species. Our work expands the list of autophagy-regulating drugs and also provides a further example of the role played by the inhibition of autophagy in breast cancer cell death. Moreover, the compounds studied may represent attractive and promising targets for subsequent molecular modeling for anti-neoplastic agents in malignant breast cancer.
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