scholarly journals Calcium carbonate nanoparticles stimulate cancer cell reprogramming to suppress tumor growth and invasion in an organ-on-a-chip system

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sandra F. Lam ◽  
Kevin W. Bishop ◽  
Rachel Mintz ◽  
Lei Fang ◽  
Samuel Achilefu
Keyword(s):  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Culture Media ◽  
Metabolic Reprogramming ◽  
Cellular Migration ◽  
Cell Culture Media ◽  
Effects Of Ph ◽  
Tumor Viability ◽  
And Behavior ◽  
And Control

AbstractThe acidic microenvironment of solid tumors induces the propagation of highly invasive and metastatic phenotypes. However, simulating these conditions in animal models present challenges that confound the effects of pH modulators on tumor progression. To recapitulate the tumor microenvironment and isolate the effect of pH on tumor viability, we developed a bifurcated microfluidic device that supports two different cell environments for direct comparison. RFP-expressing breast cancer cells (MDA-MB-231) were cultured in treatment and control chambers surrounded by fibrin, which received acid-neutralizing CaCO3 nanoparticles (nanoCaCO3) and cell culture media, respectively. Data analysis revealed that nanoCaCO3 buffered the pH within the normal physiological range and inhibited tumor cell proliferation compared to the untreated control (p < 0.05). Co-incubation of cancer cells and fibroblasts, followed by nanoCaCO3 treatment showed that the nanoparticles selectively inhibited the growth of the MDA-MB-231 cells and reduced cellular migration of these cells with no impact on the fibroblasts. Sustainable decrease in the intracellular pH of cancer cells treated with nanoCaCO3 indicates that the extracellular pH induced cellular metabolic reprogramming. These results suggest that the nanoCaCO3 can restrict the aggressiveness of tumor cells without affecting the growth and behavior of the surrounding stromal cells.

scholarly journals Calcium Carbonate Nanoparticles Stimulate Cancer Cell Reprogramming to Suppress Tumor Growth and Invasion in an Organ-on-a-chip System

2020 ◽  
Author(s):  
Sandra Lam ◽  
Kevin Bishop ◽  
Rachel Mintz ◽  
Lei Fang ◽  
Samuel Achilefu
Keyword(s):  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Culture Media ◽  
Metabolic Reprogramming ◽  
Cellular Migration ◽  
Cell Culture Media ◽  
Effects Of Ph ◽  
Tumor Viability ◽  
And Behavior ◽  
And Control

Abstract The acidic microenvironment of solid tumors induces the propagation of highly invasive and metastatic phenotypes. However, simulating these conditions in animal models present challenges that confound the effects of pH modulators on tumor progression. To recapitulate the tumor microenvironment and isolate the effect of pH on tumor viability, we developed a bifurcated microfluidic device that supports two different cell environments for direct comparison. RFP-expressing breast cancer cells (MDA-MB-231) were cultured in treatment and control chambers surrounded by fibrin, which received acid-neutralizing CaCO3 nanoparticles (nanoCaCO3) and cell culture media, respectively. Data analysis revealed that nanoCaCO3 buffered the pH within the normal physiological range and inhibited tumor cell proliferation compared to the untreated control (p < 0.05). Co-incubation of cancer cells and fibroblasts, followed by nanoCaCO3 treatment showed that the nanoparticles selectively inhibited the growth of the MDA-MB-231 cells and reduced cellular migration of these cells with no impact on the fibroblasts. Sustainable decrease in the intracellular pH of cancer cells treated with nanoCaCO3 indicates that the extracellular pH induced cellular metabolic reprogramming. These results suggest that the nanoCaCO3 can restrict the aggressiveness of tumor cells without affecting the growth and behavior of the surrounding stromal cells.

scholarly journals Interaction between CD36 and FABP4 modulates adipocyte-induced fatty acid import and metabolism in breast cancer

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Jones Gyamfi ◽  
Joo Hye Yeo ◽  
Doru Kwon ◽  
Byung Soh Min ◽  
Yoon Jin Cha ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Fatty Acid ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Tumour Microenvironment ◽  
Metabolic Reprogramming ◽  
De Novo Lipogenesis ◽  
Mesenchymal Transition ◽  
Genetic Ablation ◽  
Cd36 Expression

AbstractAdipocytes influence breast cancer behaviour via fatty acid release into the tumour microenvironment. Co-culturing human adipocytes and breast cancer cells increased CD36 expression, with fatty acid import into breast cancer cells. Genetic ablation of CD36 attenuates adipocyte-induced epithelial-mesenchymal transition (EMT) and stemness. We show a feedforward loop between CD36 and STAT3; where CD36 activates STAT3 signalling and STAT3 binds to the CD36 promoter, regulating its expression. CD36 expression results in metabolic reprogramming, with a shift towards fatty acid oxidation. CD36 inhibition induces de novo lipogenesis in breast cancer cells. Increased CD36 expression occurs with increased FABP4 expression. We showed that CD36 directly interacts with FABP4 to regulate fatty acid import, transport, and metabolism. CD36 and FABP4 inhibition induces apoptosis in tumour cells. These results indicate that CD36 mediates fatty acid import from adipocytes into cancer cells and activates signalling pathways that drive tumour progression. Targeting CD36 may have a potential for therapy, which will target the tumour microenvironment.

Effects of the Gold Nanoparticles (AuNPs) on the Proliferation and Morphological Characteristics of Human Breast Cancer Cells (MCF-7) in Culture

2017 ◽  
Vol 268 ◽  
pp. 254-258 ◽  
Author(s):  
Nur Shafawati Rosli ◽  
Azhar Abdul Rahman ◽  
Azlan Abdul Aziz ◽  
Shaharum Shamsuddin ◽  
Nurul Sabihah Zakaria
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Culture Media ◽  
Morphological Changes ◽  
Morphological Characteristics ◽  
Morphological Observation ◽  
Duration Of Treatment ◽  
Significant Difference ◽  
Mcf 7

Ultrastructural characteristic and morphological changes of untreated and treated breast cancer MCF-7 cells were observed by energy-filtered transmission electron microscope (EFTEM). Morphological observation of MCF-7 after being treated with 13 nm, 50 nm, and 70 nm AuNPs, were looking unhealthy and dying out of the populace, the observed cells were more reduced and dying as treatment with 50 nm and 70 nm AuNPs. Cells detachment, clumping, shrunken, and dispersed cells in the culture medium and floating cells were also observed. The observed morphological changes increase in 50 nm and 70 nm AuNPs than in 13 nm AuNPs, which is less toxic to MCF-7 cells. The presented morphological analysis has established that 13 nm AuNPs showed less toxic to MCF-7 breast cancer cells. Whereas, control cells of MCF-7 were treated with only complete culture media, despite the duration of treatment, whereby the cells maintained most of their morphological features and observed to have a typical morphology of healthy cells that are well attached to the surface. These results indicate that AuNPs were clustered in the cells and there was no significant difference between images of different sizes of AuNPs observed in the cells, because the AuNPs always clustered together inside the cells.

scholarly journals Bergapten induces metabolic reprogramming in breast cancer cells

2015 ◽  
Vol 35 (1) ◽  
pp. 568-576 ◽  
Author(s):  
MARTA SANTORO ◽  
CARMELA GUIDO ◽  
FRANCESCA DE AMICIS ◽  
DIEGO SISCI ◽  
ERIKA CIONE ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Metabolic Reprogramming

scholarly journals Typhonium flagelliforme decreases telomerase expression in HeLa cervical cancer cells

2016 ◽  
Vol 35 (1) ◽  
pp. 3
Author(s):  
Endang Purwaningsih ◽  
Yulia Suciati ◽  
Etty Widayanti
Keyword(s):  
Breast Cancer ◽  
Cervical Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Culture Media ◽  
Vero Cells ◽  
Telomerase Activity ◽  
Multiple Comparison Test ◽  
Cervical Cancer Cells ◽  
Experimental Laboratory

<p><strong>Background</strong><br /> Cancer cells have a relatively high telomerase activity compared to normal cells, so that cancer cells have the ability for continued proliferation and uncontrolled mitosis. Telomerase is an enzyme responsible for the length of telomeres, DNA segments located at the ends of eukaryotic chromosomes. Natural materials such as rodent tuber (<em>Typhonium flagelliforme</em>) have anticancer potential. The purpose of the present study was to determine the effects of <em>Typhonium flagelliforme </em>extract on telomerase expression in HeLa cervical cancer and T47D breast cancer cells.</p><p><br /> <strong>Methods </strong></p><p>This experimental laboratory study was conducted on cultured HeLa and T47D cancer cell lines, with normal Vero cells as controls, and using RPMI and M199 culture media. The study comprised three groups, i.e. controls, and groups receiving <em>Typhonium flagelliforme </em>extract at doses of ½ IC50 and IC50. Telomerase expression was measured by immunohistochemistry (IHC). Analysis of variance and LSD multiple comparison test were used to analyze the data.</p><p><strong> </strong></p><p><strong>Results </strong><br /> Telomerase expression in cancer cells showed significantly higher values compared to normal Vero cells. <em>Typhonium flagelliforme</em> extract was capable of significantly decreasing telomerase expression in cancer cells receiving the extract.</p><p><strong> </strong></p><strong>Conclusion </strong><br /> <em>Typhonium flagelliforme</em> extract at different doses is capable of decreasing telomerase expression more effectively in cervical cancer cells than in breast cancer cells. This study shows that <em>Typhonium flagelliforme</em> may have anti-cancer activity, necessitating further investigations.

scholarly journals Nucleotide de novo synthesis increases breast cancer stemness and metastasis via cGMP-PKG-MAPK signaling pathway

PLoS Biology ◽  
2020 ◽  
Vol 18 (11) ◽  
pp. e3000872
Author(s):  
Yajing Lv ◽  
Xiaoshuang Wang ◽  
Xiaoyu Li ◽  
Guangwei Xu ◽  
Yuting Bai ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Breast Cancer Cells ◽  
Cancer Metastasis ◽  
De Novo ◽  
Metastatic Breast ◽  
Metabolic Reprogramming ◽  
De Novo Synthesis

Metabolic reprogramming to fulfill the biosynthetic and bioenergetic demands of cancer cells has aroused great interest in recent years. However, metabolic reprogramming for cancer metastasis has not been well elucidated. Here, we screened a subpopulation of breast cancer cells with highly metastatic capacity to the lung in mice and investigated the metabolic alternations by analyzing the metabolome and the transcriptome, which were confirmed in breast cancer cells, mouse models, and patients’ tissues. The effects and the mechanisms of nucleotide de novo synthesis in cancer metastasis were further evaluated in vitro and in vivo. In our study, we report an increased nucleotide de novo synthesis as a key metabolic hallmark in metastatic breast cancer cells and revealed that enforced nucleotide de novo synthesis was enough to drive the metastasis of breast cancer cells. An increased key metabolite of de novo synthesis, guanosine-5'-triphosphate (GTP), is able to generate more cyclic guanosine monophosphate (cGMP) to activate cGMP-dependent protein kinases PKG and downstream MAPK pathway, resulting in the increased tumor cell stemness and metastasis. Blocking de novo synthesis by silencing phosphoribosylpyrophosphate synthetase 2 (PRPS2) can effectively decrease the stemness of breast cancer cells and reduce the lung metastasis. More interestingly, in breast cancer patients, the level of plasma uric acid (UA), a downstream metabolite of purine, is tightly correlated with patient’s survival. Our study uncovered that increased de novo synthesis is a metabolic hallmark of metastatic breast cancer cells and its metabolites can regulate the signaling pathway to promote the stemness and metastasis of breast cancer.

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