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.

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.

Resveratrol induces apoptosis and attenuates proliferation of MCF-7 cells in combination with radiation and hyperthermia.

2020 ◽  
Vol 20 ◽  
Author(s):  
Peyman Amini ◽  
Saeedeh Jafari Nodooshan ◽  
Milad Ashrafizadeh ◽  
Seyed-Mohammad Eftekhari ◽  
Tayebeh Aryafar ◽  
...  
Keyword(s):  
Cancer Cells ◽  
In Vitro Study ◽  
Cancer Cell Death ◽  
Radiotherapy Alone ◽  
Apoptotic Genes ◽  
Effects Of Radiation ◽  
Sensitizing Effect ◽  
Apoptosis And Necrosis ◽  
Mcf 7

Aim: In the current in vitro study, we tried to examine the possible role of resveratrol as a sensitizer in combination with radiotherapy or hyperthermia. Background: Breast cancer is the most common malignancy for women and one of the most common worldwide. It has been suggested that using non-invasive radiotherapy alone cannot eliminate cancer cells. Hyperthermia which is an adjuvant modality induces cancer cell death mainly through apoptosis and necrosis. However, cancer cells can also develop resistance to this modality. Objective: The objective of this study was to determine possible potentiation of apoptosis when MCF-7 cells treated with resveratrol before hyperthermia or radiotherapy. Method: MCF-7 cancer cells were treated with different doses of resveratrol to achieve IC50%. Afterwards, cells treated with the achieved concentration of resveratrol were exposed to radiation or hyperthermia. Proliferation, apoptosis and the expression of pro-apoptotic genes were evaluated using flow cytometry, MTT assay and real-time PCR. Results for each combination therapy were compared to radiotherapy or hyperthermia without resveratrol. Results: Both irradiation or hyperthermia could reduce viability of MCF-7 cells. Furthermore, the regulation of Bax and caspase genes increased, while Bcl-2 gene expression reduced. Resveratrol potentiated the effects of radiation and hyperthermia on MCF-7 cells. Conclusion: Results of this study suggest that resveratrol is able to induce the regulation of pro-apoptotic genes and attenuate the viability of MCF-7 cells. This may indicate the sensitizing effect of resveratrol in combination with both radiotherapy and hyperthermia.

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.

Cytotoxic Effect of the Combination of Gemcitabine and Atorvastatin Loaded in Microemulsion on the HCT116 Colon Cancer Cells

2017 ◽  
Vol 9 (2) ◽  
Author(s):  
Mayson H. Alkhatib ◽  
Dalal Al-Saedi ◽  
Wadiah S. Backer
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Anticancer Drugs ◽  
Therapeutic Potential ◽  
Morphological Changes ◽  
In Vitro Study ◽  
Colon Cancer Cells ◽  
Apoptosis Detection ◽  
Hct116 Cells

The combination of anticancer drugs in nanoparticles has great potential as a promising strategy to maximize efficacies by eradicating resistant, reduce the dosage of the drug and minimize toxicities on the normal cells. Gemcitabine (GEM), a nucleoside analogue, and atorvastatin (ATV), a cholesterol lowering agent, have shown anticancer effect with some limitations. The objective of this in vitro study was to evaluate the antitumor activity of the combination therapy of GEM and ATVencapsulated in a microemulsion (ME) formulation in the HCT116 colon cancer cells. The cytotoxicity and efficacy of the formulation were assessed by the 3- (4,5dimethylthiazole-2-yl)-2,5-diphyneltetrazolium bromide (MTT) assay. The mechanism of cell death was examined by observing the morphological changes of treated cells under light microscope, identifying apoptosis by using the ApopNexin apoptosis detection kit, and viewing the morphological changes in the chromatin structure stained with 4′,6-diamidino-2-phenylindole (DAPI) under the inverted fluorescence microscope. It has been found that reducing the concentration of GEM loaded on ME (GEM-ME) from 5μM to 1.67μM by combining it with 3.33μM of ATV in a ME formulation (GEM/2ATV-ME) has preserved the strong cytotoxicity of GEM-ME against HCT116 cells. The current study proved that formulating GEM with ATV in ME has improved the therapeutic potential of GEM and ATV as anticancer drugs.

In vitro study of doxorubicin-loaded thermo- and pH-tunable carriers for targeted drug delivery to liver cancer cells

2021 ◽  
Vol 104 ◽  
pp. 93-105
Author(s):  
Sikhumbuzo Charles Kunene ◽  
Kuen-Song Lin ◽  
Meng-Tzu Weng ◽  
Maria Janina Carrera Espinoza ◽  
Chun-Ming Wu
Keyword(s):  
Drug Delivery ◽  
Liver Cancer ◽  
Cancer Cells ◽  
Targeted Drug Delivery ◽  
In Vitro Study ◽  
Vitro Study ◽  
Liver Cancer Cells ◽  
Targeted Drug

scholarly journals Targeted delivery of mesoporous silica nanoparticles loaded monastrol into cancer cells: an in vitro study

2017 ◽  
Vol 7 (8) ◽  
pp. 549-555 ◽  
Author(s):  
Huzaifa Hanif ◽  
Samina Nazir ◽  
Kehkashan Mazhar ◽  
Muhammad Waseem ◽  
Shazia Bano ◽  
...  
Keyword(s):  
Mesoporous Silica ◽  
Silica Nanoparticles ◽  
Cancer Cells ◽  
Targeted Delivery ◽  
Mesoporous Silica Nanoparticles ◽  
In Vitro Study ◽  
Vitro Study

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.

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