scholarly journals Anti-Tumor Activity of Metformin in Human Epidermal Growth Factor Receptor 2 Positive Breast Cancer Cells

2021 ◽  
Vol 50 (5) ◽  
pp. 1393-1405
Author(s):  
Fathul Huda Fathul Huda ◽  
Sari Ekawati Sari Ekawati ◽  
Anindy Putri Addina Anindy Putri Addina ◽  
Ahmad Faried Ahmad Faried ◽  
Afiat Berbudi Afiat Berbudi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cell Death ◽  
Epidermal Growth Factor Receptor ◽  
Cell Migration ◽  
Growth Factor ◽  
Clonogenic Assay ◽  
Growth Factor Receptor ◽  
Colony Number ◽  
Epidermal Growth

Breast Cancer (BC) is the leading cause of cancer death in women. One BC subtype is very aggressive with amplification of human epidermal growth factor receptor 2 (HER2) protein. Although specific HER2+ targeting agents are available, most of HER2+ BC patients develop resistant to these agents. Recent studies show that metformin, is able to become anti-tumor in various cancer cells. This research aims to evaluate anti-tumor activities of metformin to HER2+ BC cells in both sensitive and resistant to trastuzumab. A series of assays were performed to evaluate metformin anti-tumor activities in HCC-1954 and SKBR-3 HER2+ BC cells. MTT assay was performed to evaluate cell death, and inhibitory concentration (IC50), while scratch assay was performed to assess inhibition of cell migration and clonogenic assay to assess cell proliferation. p<0.05 was considered to be significant. Metformin could suppress the number of HER2+ BC cells. Viability assay showed suppression of viable cells after metformin incubation of 60 and 600 µM compared to control, 30 and 90%, respectively. Surprisingly, IC50 of metformin was smaller in HER2+ BC HCC-1954 cells that resistant to trastuzumab compare to the sensitive one (SKBR-3). Both were below 1 µM, with R2 more than 0.95. Additionally, clonogenic assay showed less colony number and colony area with at least p < 0.05 in colony number and p < 0.01 in the area. In addition, metformin inhibited cell migration of HER2+ BC cells. Metformin shows a potency as anti-tumor by inducing cell death, inhibiting cell proliferation and cell migration of HER2+ BC cells.

Requirement of the epidermal growth factor receptor in renal epithelial cell proliferation and migration

2004 ◽  
Vol 287 (3) ◽  
pp. F365-F372 ◽  
Author(s):  
Shougang Zhuang ◽  
Yujing Dang ◽  
Rick G. Schnellmann
Keyword(s):  
Cell Proliferation ◽  
Epidermal Growth Factor Receptor ◽  
Cell Migration ◽  
Growth Factor ◽  
Growth Factor Receptor ◽  
Mechanical Injury ◽  
Cell Proliferation And Migration ◽  
Epidermal Growth ◽  
And Migration ◽  
Proliferation And Migration

We showed that renal proximal tubular cells (RPTC) can proliferate and migrate following plating and oxidant or mechanical injury in the absence of exogenous growth factors; however, the mechanisms of this response remain unclear. We examined whether epidermal growth factor receptor (EGFR) signaling is activated following plating and mechanical injury and mediates RPTC proliferation and migration. EGFR, Akt [a target of phosphoinositide-3-kinase (PI3K)], and ERK1/2 were activated after plating and mechanical injury, and their phosphorylation was further enhanced by addition of exogenous EGF. Inactivation of the EGFR with the selective inhibitor AG-1478 completely blocked phosphorylation of EGFR, Akt, and ERK1/2 and blocked cell proliferation and migration after plating and injury. Inhibition of PI3K with LY-294002 blocked Akt phosphorylation and proliferation, whereas U-0126 blocked ERK1/2 phosphorylation but had no effect on proliferation. Furthermore, p38 was phosphorylated following mechanical injury and the p38 inhibitor SB-203580 blocked p38 phosphorylation and cell migration. In contrast, neither PI3K nor ERK1/2 inhibition blocked cell migration. These results show that EGFR activation is required for RPTC proliferation and migration and that proliferation is mediated by PI3K, whereas migration is mediated by p38.

scholarly journals Triptolide Decreases Cell Proliferation and Induces Cell Death in Triple Negative MDA-MB-231 Breast Cancer Cells

Biomolecules ◽  
2018 ◽  
Vol 8 (4) ◽  
pp. 163 ◽  
Author(s):  
Elizabeth Varghese ◽  
Samson Samuel ◽  
Sharon Varghese ◽  
Sohaila Cheema ◽  
Ravinder Mamtani ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Death ◽  
Estrogen Receptor ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Caspase 3 ◽  
Triple Negative ◽  
Growth Factor Receptor ◽  
Epidermal Growth

Triple negative breast cancers (TNBCs) do not respond to conventional estrogen receptor/progesterone receptor/human epidermal growth factor receptor-2 targeted interventions due to the absence of the respective receptor targets. They are aggressive, exhibit early recurrence, metastasize, are more invasive in nature, and develop drug resistance. Some plant-derived substances have been screened and have gained attention as efficient anticancer drugs for TNBCs with few adverse effects. Here, we evaluate triptolide (concentrations in the range of 100 pM to 10 µM), a di-terpene tri-epoxide isolated from thunder god vine for its efficacy as anticancer drug in MDA-MB-231 TNBC cells. Cell proliferation and viability were assessed using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) (MTS) assay and trypan blue exclusion assay, respectively. A flow cytometry-based apoptosis assay was performed by using fluorescein isothiocyanate (FITC)-conjugated annexin V and propidium iodide (PI). Western blotting was performed to determine the levels of apoptotic and autophagy proteins such as caspase 3, LC3B and SQSTM1/p62. Results indicate that in 72 h of 1 nM triptolide treatment, the percentage of cell proliferation in MDA-MB-231 cells declined to 49 ± 18.9% (mean ± standard deviation (SD)), whereas the proliferation rate did not drop below 80% in MCF-7 cells (non-TNBC cells which express the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2) even at the highest concentration tested (10 µM). The MDA-MB-468 cells showed a similar trend to MDA-MB-231 cells. Furthermore, triptolide treatment for 72 h significantly decreased cell viability at concentrations above 10 nM. Apoptotic cell death assay in 72 h triptolide-treated MDA-MB-231 cells revealed 29.3 ± 10.57% of early apoptotic cells in comparison to the control group (4.61 ± 2.24%). Cell cycle analysis indicated accumulation of cells in sub G0/G1 phase, indicating apoptosis. Western blot analysis in the 25 nM triptolide treatment group revealed induction of autophagy as shown by a significant decrease in the levels of autophagy marker p62 (by 0.2-fold p < 0.0001) and with an increase in the levels of LC3B-II (by 8-fold p < 0.05). An increase in the levels of the apoptotic marker cleaved caspase 3 (by 4-fold p < 0.05) was also observed in triptolide treated MDA-MB-231 cells. Our data shows that triptolide could be an efficient anticancer agent in the treatment of TNBCs.

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