Modulation of translation factor's gene expression by histone deacetylase inhibitors in breast cancer cells

AbstractThe histone deacetylase inhibitors sodium butyrate (NaBu) and trichostatin A (TSA) exhibit anti-proliferative activity by causing cell cycle arrest and apoptosis. The mechanisms by which NaBu and TSA cause apoptosis and cell cycle arrest are not yet completely clarified, although these agents are known to modulate the expression of several genes including cell-cycle- and apoptosis-related genes. The enzymes involved in the process of translation have important roles in controlling cell growth and apoptosis, and several of these translation factors have been described as having a causal role in the development of cancer. The expression patterns of the translation mechanism, namely of the elongation factors eEF1A1 and eEF1A2, and of the termination factors eRF1 and eRF3, were studied in the breast cancer cell line MCF-7 by real-time quantitative reverse transcription-polymerase chain reaction after a 24-h treatment with NaBu and TSA. NaBu induced inhibition of translation factors' transcription, whereas TSA caused an increase in mRNA levels. Thus, these two agents may modulate the expression of translation factors through different pathways. We propose that the inhibition caused by NaBu may, in part, be responsible for the cell cycle arrest and apoptosis induced by this agent in MCF-7 cells.

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Downregulation of RBBP6 variant 1 during arsenic trioxide-mediated cell cycle arrest and curcumin-induced apoptosis in MCF-7 breast cancer cells

Future Science OA ◽

10.2144/fsoa-2019-0047 ◽

2019 ◽

Vol 5 (8) ◽

pp. FSO409

Author(s):

Lilian Makgoo ◽

Kagiso Laka ◽

Zukile Mbita

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Cell Cycle Arrest ◽

Arsenic Trioxide ◽

Breast Cancer Cells ◽

Expression Patterns ◽

Rt Pcr ◽

Cycle Arrest ◽

Induced Apoptosis ◽

Mcf 7

Aim: To determine the expression patterns of the RBBP6 spliced variants during arsenic trioxide-mediated cell cycle arrest and curcumin-induced apoptosis in MCF-7 cells. Materials & methods: As2O3 and curcumin were used to study cytotoxicity, cell cycle arrest, apoptosis and the expression of RBBP6 variants. The MUSE Cell Analyser was used to analyze cell cycle arrest, apoptosis and multicaspase activity while apoptosis was further confirmed using microscopy. Semi-quantitative RT-PCR was employed to quantitate the expression of the RBBP6 variants. Results: This study showed that the MCF-7 cells expressed RBBP6 variant 1 but lacked both variant 2 and variant 3. Both As2O3 and curcumin significantly downregulated RBBP6 variant 1 (p < 0.001). Conclusion: RBBP6 variants are promising therapeutic targets.

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Mutant p53L194F Harboring Luminal-A Breast Cancer Cells Are Refractory to Apoptosis and Cell Cycle Arrest in Response to MortaparibPlus, a Multimodal Small Molecule Inhibitor

Cancers ◽

10.3390/cancers13123043 ◽

2021 ◽

Vol 13 (12) ◽

pp. 3043

Author(s):

Ahmed Elwakeel ◽

Anissa Nofita Sari ◽

Jaspreet Kaur Dhanjal ◽

Hazna Noor Meidinna ◽

Durai Sundar ◽

...

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Cell Cycle Arrest ◽

Cancer Cells ◽

Small Molecule ◽

Breast Cancer Cells ◽

Luminal A ◽

Molecular Analyses ◽

Cycle Arrest ◽

Mcf 7

We previously performed a drug screening to identify a potential inhibitor of mortalin–p53 interaction. In four rounds of screenings based on the shift in mortalin immunostaining pattern from perinuclear to pan-cytoplasmic and nuclear enrichment of p53, we had identified MortaparibPlus (4-[(1E)-2-(2-phenylindol-3-yl)-1-azavinyl]-1,2,4-triazole) as a novel synthetic small molecule. In order to validate its activity and mechanism of action, we recruited Luminal-A breast cancer cells, MCF-7 (p53wild type) and T47D (p53L194F) and performed extensive biochemical and immunocytochemical analyses. Molecular analyses revealed that MortaparibPlus is capable of abrogating mortalin–p53 interaction in both MCF-7 and T47D cells. Intriguingly, upregulation of transcriptional activation function of p53 (as marked by upregulation of the p53 effector gene—p21WAF1—responsible for cell cycle arrest and apoptosis) was recorded only in MortaparibPlus-treated MCF-7 cells. On the other hand, MortaparibPlus-treated T47D cells exhibited hyperactivation of PARP1 (accumulation of PAR polymer and decrease in ATP levels) as a possible non-p53 tumor suppression program. However, these cells did not show full signs of either apoptosis or PAR-Thanatos. Molecular analyses attributed such a response to the inability of MortaparibPlus to disrupt the AIF–mortalin complexes; hence, AIF did not translocate to the nucleus to induce chromatinolysis and DNA degradation. These data suggested that the cancer cells possessing enriched levels of such complexes may not respond to MortaparibPlus. Taken together, we report the multimodal anticancer potential of MortaparibPlus that warrants further attention in laboratory and clinical studies.

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Human somatostatin receptor-3 distinctively induces apoptosis in MCF-7 and cell cycle arrest in MDA-MB-231 breast cancer cells

Molecular and Cellular Endocrinology ◽

10.1016/j.mce.2015.06.019 ◽

2015 ◽

Vol 413 ◽

pp. 129-144 ◽

Cited By ~ 15

Author(s):

Sajad A. War ◽

Brian Kim ◽

Ujendra Kumar

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Cell Cycle Arrest ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Somatostatin Receptor ◽

Cycle Arrest ◽

Mcf 7

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Histone deacetylase inhibitors trichostatin A and valproic acid induce cell cycle arrest and p21 expression in immortalized human endometrial stromal cells

European Journal of Obstetrics & Gynecology and Reproductive Biology ◽

10.1016/j.ejogrb.2007.02.014 ◽

2008 ◽

Vol 137 (2) ◽

pp. 198-203 ◽

Cited By ~ 41

Author(s):

Yan Wu ◽

Sun-Wei Guo

Keyword(s):

Cell Cycle ◽

Valproic Acid ◽

Cell Cycle Arrest ◽

Histone Deacetylase ◽

Stromal Cells ◽

Histone Deacetylase Inhibitors ◽

Trichostatin A ◽

Induce Cell Cycle Arrest ◽

Endometrial Stromal Cells ◽

Cycle Arrest

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Calcitriol and menadione produces cell cycle arrest, oxidative and nitrosative stress, mitochondrial damage and cell death on MCF-7 breast cancer cell

Bone ◽

10.1016/j.bone.2015.12.032 ◽

2016 ◽

Vol 89 ◽

pp. 67

Author(s):

S. Guizzardi ◽

G. Picotto ◽

V. Rodríguez ◽

L. Bohl ◽

N. Tolosa de Talamoni

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Cell Death ◽

Cell Cycle Arrest ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Nitrosative Stress ◽

Oxidative And Nitrosative Stress ◽

Cycle Arrest ◽

Mcf 7

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Thymoquinone-Loaded Nanostructured Lipid Carrier Exhibited Cytotoxicity towards Breast Cancer Cell Lines (MDA-MB-231 and MCF-7) and Cervical Cancer Cell Lines (HeLa and SiHa)

BioMed Research International ◽

10.1155/2015/263131 ◽

2015 ◽

Vol 2015 ◽

pp. 1-10 ◽

Cited By ~ 28

Author(s):

Wei Keat Ng ◽

Latifah Saiful Yazan ◽

Li Hua Yap ◽

Wan Abd Ghani Wan Nor Hafiza ◽

Chee Wun How ◽

...

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Cervical Cancer ◽

Cell Cycle Arrest ◽

Cell Lines ◽

Cancer Cell ◽

Cancer Cell Lines ◽

Nanostructured Lipid Carrier ◽

Cycle Arrest ◽

Mcf 7

Thymoquinone (TQ) has been shown to exhibit antitumor properties. Thymoquinone-loaded nanostructured lipid carrier (TQ-NLC) was developed to improve the bioavailability and cytotoxicity of TQ. This study was conducted to determine the cytotoxic effects of TQ-NLC on breast cancer (MDA-MB-231 and MCF-7) and cervical cancer cell lines (HeLa and SiHa). TQ-NLC was prepared by applying the hot high pressure homogenization technique. The mean particle size of TQ-NLC was 35.66 ± 0.1235 nm with a narrow polydispersity index (PDI) lower than 0.25. The zeta potential of TQ-NLC was greater than −30 mV. Polysorbate 80 helps to increase the stability of TQ-NLC. Differential scanning calorimetry showed that TQ-NLC has a melting point of 56.73°C, which is lower than that of the bulk material. The encapsulation efficiency of TQ in TQ-NLC was 97.63 ± 0.1798% as determined by HPLC analysis. TQ-NLC exhibited antiproliferative activity towards all the cell lines in a dose-dependent manner which was most cytotoxic towards MDA-MB-231 cells. Cell shrinkage was noted following treatment of MDA-MB-231 cells with TQ-NLC with an increase of apoptotic cell population (P<0.05). TQ-NLC also induced cell cycle arrest. TQ-NLC was most cytotoxic towards MDA-MB-231 cells. It induced apoptosis and cell cycle arrest in the cells.

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