Polyamines modulate the roscovitine-induced cell death switch decision autophagy vs. apoptosis in MCF-7 and MDA-MB-231 breast cancer cells

Macrophage colony-stimulating factor is a vital factor in maintaining the biological function of monocyte–macrophage lineage. It is expressed in many tumor tissues and cancer cells. Recent findings indicate that macrophage colony-stimulating factor might contribute to chemoresistance, but the precise mechanisms are unclear. This study was to explore the effect of macrophage colony-stimulating factor on doxorubicin resistance in MCF-7 breast cancer cells and the possible mechanism. In the study, the human breast cancer cells, MCF-7, were transfected with macrophage colony-stimulating factor. We document that cytoplasmic macrophage colony-stimulating factor induces doxorubicin resistance and inhibits apoptosis in MCF-7 cells. Further studies demonstrated that cytoplasmic macrophage colony-stimulating factor-mediated apoptosis inhibition was dependent on the activation of PI3K/Akt/Survivin pathway. More importantly, we found that macrophage colony-stimulating factor-induced autophagic cell death in doxorubicin-treated MCF-7 cells. Taken together, we show for the first time that macrophage colony-stimulating factor-induced doxorubicin resistance is associated with the changes in cell death response with defective apoptosis and promotion of autophagic cell death.

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Methotrexate induced cell death mechanisms in MCF-7 adenocarcinoma breast cancer cells: Enhanced cytotoxicity following dff45-siRNA pre-treatment

Synergy ◽

10.1016/j.synres.2018.08.002 ◽

2018 ◽

Vol 7 ◽

pp. 10-16

Author(s):

Fatemeh Kiani ◽

Negin Rasouli ◽

Tahereh Kashkoolinejad ◽

Shahrokh Safarian ◽

Seyed Jalal Zargar ◽

...

Keyword(s):

Breast Cancer ◽

Cell Death ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Pre Treatment ◽

Cell Death Mechanisms ◽

Mcf 7

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HDAC3–ERα Selectively Regulates TNF-α-Induced Apoptotic Cell Death in MCF-7 Human Breast Cancer Cells via the p53 Signaling Pathway

Cells ◽

10.3390/cells9051280 ◽

2020 ◽

Vol 9 (5) ◽

pp. 1280

Author(s):

Seung-Ho Park ◽

Hyunhee Kim ◽

Sungmin Kwak ◽

Ji-Hoon Jeong ◽

Jangho Lee ◽

...

Keyword(s):

Breast Cancer ◽

Cell Death ◽

Cancer Cells ◽

Human Breast Cancer ◽

Breast Cancer Cells ◽

Apoptotic Cell ◽

Human Breast Cancer Cells ◽

Human Breast ◽

Tnf Α ◽

Mcf 7

Tumor necrosis factor-α (TNF-α) plays a significant role in inflammation and cancer-related apoptosis. We identified a TNF-α-mediated epigenetic mechanism of apoptotic cell death regulation in estrogen receptor-α (ERα)-positive human breast cancer cells. To assess the apoptotic effect of TNF-α, annexin V/ propidium iodide (PI) double staining, cell viability assays, and Western blotting were performed. To elucidate this mechanism, histone deacetylase (HDAC) activity assay and immunoprecipitation (IP) were conducted; the mechanism was subsequently confirmed through chromatin IP (ChIP) assays. Finally, we assessed HDAC3–ERα-mediated apoptotic cell death after TNF-α treatment in ERα-positive human breast cancer (MCF-7) cells via the transcriptional activation of p53 target genes using luciferase assay and quantitative reverse transcription PCR. The TNF-α-induced selective apoptosis in MCF-7 cells was negatively regulated by the HDAC3–ERα complex in a caspase-7-dependent manner. HDAC3 possessed a p53-binding element, thus suppressing the transcriptional activity of its target genes. In contrast, MCF-7 cell treatment with TNF-α led to dissociation of the HDAC3–ERα complex and substitution of the occupancy on the promoter by the p53–p300 complex, thus accelerating p53 target gene expression. In this process, p53 stabilization was accompanied by its acetylation. This study showed that p53-mediated apoptosis in ERα-positive human breast cancer cells was negatively regulated by HDAC3–ERα in a caspase-7-dependent manner. Therefore, these proteins have potential application in therapeutic strategies.

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Thymoquinone Enhances Paclitaxel Anti-Breast Cancer Activity via Inhibiting Tumor-Associated Stem Cells Despite Apparent Mathematical Antagonism

Molecules ◽

10.3390/molecules25020426 ◽

2020 ◽

Vol 25 (2) ◽

pp. 426 ◽

Cited By ~ 6

Author(s):

Hanan A. Bashmail ◽

Aliaa A. Alamoudi ◽

Abdulwahab Noorwali ◽

Gehan A. Hegazy ◽

Ghada M. Ajabnoor ◽

...

Keyword(s):

Breast Cancer ◽

Stem Cells ◽

Cell Death ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Cell Clone ◽

T47d Cells ◽

Ic50 Values ◽

Twist 1 ◽

Mcf 7

Thymoquinone (TQ) has shown substantial evidence for its anticancer effects. Using human breast cancer cells, we evaluated the chemomodulatory effect of TQ on paclitaxel (PTX). TQ showed weak cytotoxic properties against MCF-7 and T47D breast cancer cells with IC50 values of 64.93 ± 14 µM and 165 ± 2 µM, respectively. Combining TQ with PTX showed apparent antagonism, increasing the IC50 values of PTX from 0.2 ± 0.07 µM to 0.7 ± 0.01 µM and from 0.1 ± 0.01 µM to 0.15 ± 0.02 µM in MCF-7 and T47D cells, respectively. Combination index analysis showed antagonism in both cell lines with CI values of 4.6 and 1.6, respectively. However, resistance fractions to PTX within MCF-7 and T47D cells (42.3 ± 1.4% and 41.9 ± 1.1%, respectively) were completely depleted by combination with TQ. TQ minimally affected the cell cycle, with moderate accumulation of cells in the S-phase. However, a significant increase in Pre-G phase cells was observed due to PTX alone and PTX combination with TQ. To dissect this increase in the Pre-G phase, apoptosis, necrosis, and autophagy were assessed by flowcytometry. TQ significantly increased the percent of apoptotic/necrotic cell death in T47D cells after combination with paclitaxel. On the other hand, TQ significantly induced autophagy in MCF-7 cells. Furthermore, TQ was found to significantly decrease breast cancer-associated stem cell clone (CD44+/CD24-cell) in both MCF-7 and T47D cells. This was mirrored by the downregulation of TWIST-1 gene and overexpression of SNAIL-1 and SNAIL-2 genes. TQ therefore possesses potential chemomodulatory effects to PTX when studied in breast cancer cells via enhancing PTX induced cell death including autophagy. In addition, TQ depletes breast cancer-associated stem cells and sensitizes breast cancer cells to PTX killing effects.

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