scholarly journals Cell-penetrating doxorubicin released from Elastin-like polypeptide kills doxorubicin-resistant cancer cells in vitro study

2020 ◽  
Author(s):  
Jung Su Ryu ◽  
Felix Kratz ◽  
Drazen Raucher
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
In Vitro Study ◽  
Fold Increase ◽  
Membrane Penetration ◽  
Cancer Cell Death ◽  
Cell Penetrating ◽  
Resistant Cells

Abstract Background: Elastin-like polypeptide (ELP) undergoes its characteristic of phase transitioning in response to ambient temperature. ELP therefore has been be used as a thermosensitive vector for the delivery of chemotherapy agents since it can be targeted to hyperthermic tumors. This novel strategy introduces unprecedented options for treating cancer, with fewer concerns about side effects. In this study, the ELP system was further modified with an enzyme-cleavable linker in order to release drugs within tumors. This system consists of ELP, a matrix metalloproteinase (MMP) substrate, a cell penetrating peptide (CPP), and 6-maleimidocaproyl amide derivative of doxorubicin (Dox). This construct may be initially targeted to the tumor by application of mild heat after administration. Within the hyperthermic tumor, then this construct is cleaved by MMP, releasing CPP-Dox, which can infiltrate tumor tissues and penetrate cell membranes.Methods: We produced the construct in E.coli and examined its cleavage by MMP enzymes in vitro. Flow cytometry and confocal analysis were used to verify the facilitated uptake of the digested cell-penetrating Dox by breast cancer cells and Dox-resistant cells. Cytotoxicity tests further demonstrated improvements in bioavailability of cell-penetrating Dox following the enhanced cellular uptake of the cancer cells. Comparisons with the non-cleavable ELP counterpart were paralleled.Results: This strategy shows up to a 4-fold increase in cell penetration and results in more death in breast cancer cells than the ELP-Dox. Even in doxorubicin-resistant cells (NCI/ADR and MES/ADR), ELP-released, cell-penetrating doxorubicin demonstrated better membrane penetration, leading to at least twice the killing of resistant cells than ELP-Dox and free Dox. Conclusion: MMP-digested CPP-Dox shows better membrane penetration and induces more cancer cell death in vitro. This CPP-complexed Dox released from ELP kills even dox-resistant cells more efficiently than both free doxorubicin and non-cleaved ELP-CPP-Dox.

scholarly journals Cell-penetrating doxorubicin released from Elastin-like polypeptide kills doxorubicin-resistant cancer cells

2020 ◽  
Author(s):  
Jung Su Ryu ◽  
Felix Kratz ◽  
Drazen Raucher
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Fold Increase ◽  
Membrane Penetration ◽  
Cancer Cell Death ◽  
Cell Penetrating ◽  
Novel Strategy ◽  
Resistant Cells

Abstract Background: Elastin-like polypeptide (ELP) undergoes its characteristic of phase transitioning in response to ambient temperature. ELP therefore has been be used as a thermosensitive vector for the delivery of chemotherapy agents since it can be targeted to hyperthermic tumors. This novel strategy introduces unprecedented options for treating cancer, with fewer concerns about side effects. In this study, the ELP system was further modified with an enzyme-cleavable linker in order to release drugs within tumors. This system consists of ELP, a matrix metalloproteinase (MMP) substrate, a cell penetrating peptide (CPP), and 6-maleimidocaproyl amide derivative of doxorubicin (Dox). This construct may be initially targeted to the tumor by application of mild heat after administration. Within the hyperthermic tumor, then this construct is cleaved by MMP, releasing CPP-Dox, which can infiltrate tumor tissues and penetrate cell membranes. Methods: We produced the construct in E.coli and examined its cleavage by MMP enzymes in vitro. Flow cytometry and confocal analysis were used to verify the facilitated uptake of the digested cell-penetrating Dox by breast cancer cells and Dox-resistant cells. Cytotoxicity tests further demonstrated improvements in bioavailability of cell-penetrating Dox following the enhanced cellular uptake of the cancer cells. Comparisons with the non-cleavable ELP counterpart were paralleled. Results: This strategy shows up to a 4-fold increase in cell penetration and results in more death in breast cancer cells than the ELP-Dox. Even in doxorubicin-resistant cells (NCI/ADR and MES/ADR), ELP-released, cell-penetrating doxorubicin demonstrated better membrane penetration, leading to at least twice the killing of resistant cells than ELP-Dox and free Dox. Conclusion: MMP-digested CPP-Dox shows better membrane penetration and induces more cancer cell death in vitro. This CPP-complexed Dox released from ELP kills even dox-resistant cells more efficiently than both free doxorubicin and non-cleaved ELP-CPP-Dox.

scholarly journals Cell-Penetrating Doxorubicin Released from Elastin-Like Polypeptide Kills Doxorubicin-Resistant Cancer Cells in In Vitro Study

2021 ◽  
Vol 22 (3) ◽  
pp. 1126
Author(s):  
Jung Su Ryu ◽  
Felix Kratz ◽  
Drazen Raucher
Keyword(s):  
Cancer Cells ◽  
In Vitro Study ◽  
Fold Increase ◽  
Membrane Penetration ◽  
Cancer Cell Death ◽  
Cell Penetrating ◽  
Free Doxorubicin ◽  
Novel Strategy ◽  
Resistant Cells

Elastin-like polypeptides (ELPs) undergo a characteristic phase transition in response to ambient temperature. Therefore, it has been be used as a thermosensitive vector for the delivery of chemotherapy agents since it can be used to target hyperthermic tumors. This novel strategy introduces unprecedented options for treating cancer with fewer concerns about side effects. In this study, the ELP system was further modified with an enzyme-cleavable linker in order to release drugs within tumors. This system consists of an ELP, a matrix metalloproteinase (MMP) substrate, a cell-penetrating peptide (CPP), and a 6-maleimidocaproyl amide derivative of doxorubicin (Dox). This strategy shows up to a 4-fold increase in cell penetration and results in more death in breast cancer cells compared to ELP-Dox. Even in doxorubicin-resistant cells (NCI/ADR and MES-SA/Dx5), ELP-released cell-penetrating doxorubicin demonstrated better membrane penetration, leading to at least twice the killing of resistant cells compared to ELP-Dox and free Dox. MMP-digested CPP-Dox showed better membrane penetration and induced more cancer cell death in vitro. This CPP-complexed Dox released from the ELP killed even Dox-resistant cells more efficiently than both free doxorubicin and non-cleaved ELP-CPP-Dox.

Suberosin attenuates the proliferation of MCF-7 breast cancer cells in combination with radiotherapy or hyperthermia.

2020 ◽  
Vol 12 ◽  
Author(s):  
Saeedeh Jafari Nodooshan ◽  
Peyman Amini ◽  
Milad Ashrafizadeh ◽  
Saeed Tavakoli ◽  
Tayebeh Aryafar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
In Vitro Study ◽  
Therapeutic Modality ◽  
Potential Candidate ◽  
Therapeutic Efficiency ◽  
Cancer Cell Death ◽  
Mcf 7

Aim: The aim of this study was to determine the proliferation of MCF-7 following irradiation or hyperthermia as alone or pre-treatment with suberosin. Background: Radiotherapy is a major therapeutic modality for the control of breast cancer. However, hyperthermia can be prescribed for relief of pain or enhancing cancer cell death. Some studies have attempted its use as an adjuvant to improve therapeutic efficiency. Suberosin is a cumarin-derived natural agent that has shown anti-inflammatory properties. Objective: In this in vitro study, possible sensitization effect of suberosin in combination with radiation or hyperthermia was evaluated. Method: MCF-7 breast cancer cells were irradiated or received hyperthermia with or without treatment with suberosin. The incidence of apoptosis as well as viability of MCF-7 cells were observed. Furthermore, the expressions of proapoptotic genes such as Bax, Bcl-2, and some caspases were evaluated using real-time PCR. Results: Both radiotherapy or hyperthermia reduced the proliferation of MCF-7 cells. Suberosin amplified the effects of radiotherapy or hyperthermia for induction of pro-apoptotic genes and reducing cell viability. Conclusion: Suberosin has a potent anti-cancer effect when combined with radiotherapy or hyperthermia. It could be a potential candidate for killing breast cancer cells as well as increasing the therapeutic efficiency of radiotherapy or hyperthermia.

scholarly journals In Vitro Study of Breast Cancer Cells Exposed to Antisense of Liver Fatty Acid Binding Protein

2006 ◽  
Vol 20 (4) ◽  
Author(s):  
Stacy‐Ann Miller ◽  
Byron Waddy ◽  
Nabarun Chakraborty ◽  
Rasha Hammamieh ◽  
Marti Jett
Keyword(s):  
Breast Cancer ◽  
Fatty Acid ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Fatty Acid Binding Protein ◽  
In Vitro Study ◽  
Liver Fatty Acid ◽  
Fatty Acid Binding ◽  
Acid Binding Protein

scholarly journals Hydrogen Phosphate Selectively Induces MDA-MB-231 Breast Cancer Cell Death in vitro

2021 ◽  
Author(s):  
Aya Shanti ◽  
Kenana Al Adem ◽  
Cesare Stefanini ◽  
Sungmun Lee
Keyword(s):  
Breast Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Dihydrogen Phosphate ◽  
Human Breast ◽  
Hydrogen Phosphate ◽  
Cancer Cell Death ◽  
Phosphate Ions

Abstract Phosphate ions are the most abundant anions inside the cells, and they are increasingly gaining attention as key modulators of cellular function and gene expression. However, little is known about the effect of inorganic phosphate ions on cancer cells, particularly breast cancer cells. Here, we investigated the toxicity of different phosphate compounds to triple-negative human breast cancer cells (MDA-MB-231) and compared it to that of human monocytes (THP-1). We found that, unlike dihydrogen phosphate (H2PO4−), hydrogen phosphate (HPO42−) at 20 mM or lower concentrations induced breast cancer (MDA-MB-231) cell death more than immune (THP-1) cell death. We correlate this effect to the fact that phosphate in the form of HPO42− raises pH levels to alkaline levels which are not optimum for transport of phosphate into cancer cells. The results in this study highlight the importance of further exploring hydrogen phosphate (HPO42−) as a potential therapeutic for the treatment of breast cancer.

An in-vitro study of the effects of temperature on breast cancer cells: Experiments and models

2012 ◽  
Vol 32 (8) ◽  
pp. 2242-2249 ◽  
Author(s):  
C. Theriault ◽  
E. Paetzell ◽  
R. Chandrasekar ◽  
C. Barkey ◽  
Y. Oni ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
In Vitro Study ◽  
Vitro Study ◽  
Effects Of Temperature

scholarly journals An In Vitro Study of the Photodynamic Effectiveness of GO-Ag Nanocomposites against Human Breast Cancer Cells

Nanomaterials ◽  
2017 ◽  
Vol 7 (11) ◽  
pp. 401 ◽  
Author(s):  
Fozia Shaheen ◽  
Muhammad Hammad Aziz ◽  
Muhammad Fakhar-e-Alam ◽  
Muhammad Atif ◽  
Mahvish Fatima ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
In Vitro Study ◽  
Vitro Study ◽  
Human Breast Cancer Cells ◽  
Human Breast

Targeted phase-change contrast agents for intracellular delivery to breast cancer tumors: An In vitro study in MDA-MB-231 breast cancer cells

2016 ◽  
Vol 140 (4) ◽  
pp. 3371-3371
Author(s):  
Kyle P. Hadinger ◽  
Joseph P. Marshalek ◽  
Paul S. Sheeran ◽  
Pier Ingram ◽  
Russell S. Witte ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Phase Change ◽  
Contrast Agents ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
In Vitro Study ◽  
Intracellular Delivery ◽  
Vitro Study

Inhibition of 11 beta-hydroxysteroid dehydrogenase activity enhances the antiproliferative effect of glucocorticosteroids on MCF-7 and ZR-75-1 breast cancer cells

1997 ◽  
Vol 155 (1) ◽  
pp. 171-180 ◽  
Author(s):  
S Hundertmark ◽  
H Buhler ◽  
M Rudolf ◽  
HK Weitzel ◽  
V Ragosch
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
In Vitro Study ◽  
Hydroxysteroid Dehydrogenase ◽  
Antiproliferative Effect ◽  
Continuous Exposure ◽  
Antiproliferative Action ◽  
Mcf 7

This in vitro study on MCF-7 and ZR-75-1 breast cancer cells showed that the antiproliferative action of glucocorticosteroids (GCS) on breast cancer cells is weakened by a high oxidative activity of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD; EC 1.1.1.146): both endogenic as well as synthetic GCS (dexamethasone, prednisolone) were metabolised to hormonally inactive 11-dehydro metabolites. This enzymatic shield protected the breast cancer cells from the antiproliferative action of GCS. Continuous exposure of breast cancer cells to GCS resulted in enhanced 11 beta-HSD activity. The intracellular GCS concentration was further reduced by this feedback and thus the antiproliferative effect was additionally weakened. These mechanisms of GCS deactivation could be influenced by inhibiting 11 beta-HSD with the liquorice compound glycyrrhetinic acid (GLY). In MCF-7 and ZR-75-1 cultures the antiproliferative effect of GCS was significantly increased by GLY.

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