scholarly journals A pH-Sensitive, Biobased Calcium Carbonate Aragonite Nanocrystal as a Novel Anticancer Delivery System

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Abdullahi Shafiu Kamba ◽  
Maznah Ismail ◽  
Tengku Azmi Tengku Ibrahim ◽  
Zuki Abu Bakar Zakaria
Keyword(s):  
Breast Cancer ◽  
Calcium Carbonate ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Slow Release ◽  
Neutral Red ◽  
Target Cells ◽  
Cancer Cell Death ◽  
Effective Carrier

The synthesised biobased calcium carbonate nanocrystals had demonstrated to be an effective carrier for delivery of anticancer drug doxorubicin (DOX). The use of these nanocrystals displayed high levels of selectivity and specificity in achieving effective cancer cell death without nonspecific toxicity. These results confirmed that DOX was intercalated into calcium carbonate nanocrystals at high loading and encapsulation efficiency (4.8 and 96%, resp.). The CaCO3/DOX nanocrystals are relatively stable at neutral pH (7.4), resulting in slow release, but the nanocrystals progressively dissociated in acidic pH (4.8) regimes, triggering faster release of DOX. The CaCO3/DOX nanocrystals exhibited high uptake by MDA MB231 breast cancer cells and a promising potential delivery of DOX to target cells.In vitrochemosensitivity using MTT, modified neutral red/trypan blue assay, and LDH on MDA MB231 breast cancer cells revealed that CaCO3/DOX nanocrystals are more sensitive and gave a greater reduction in cell growth than free DOX. Our findings suggest that CaCO3nanocrystals hold tremendous promise in the areas of controlled drug delivery and targeted cancer therapy.

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.

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.

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 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 Immunoliposomes with Simvastatin as a Potential Therapeutic in Treatment of Breast Cancer Cells Overexpressing HER2—An In Vitro Study

Cancers ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 418 ◽  
Author(s):  
Lucyna Matusewicz ◽  
Joanna Podkalicka ◽  
Aleksander Sikorski
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Growth Factor Receptor ◽  
In Vitro Study ◽  
Anticancer Therapy ◽  
Signalling Pathways ◽  
Target Cells ◽  
The Stability

Lipophilic statins are promising candidates for breast cancer treatment. However, anticancer therapy requires much higher doses of statins than can be delivered orally, and such high doses are known to exert more adverse effects. The main objective of our study was to design a targeted, therapeutic liposomal carrier of simvastatin characterised by high stability and specificity towards breast cancer cells. We chose SKBR3, the cell line that showed the highest sensitivity for simvastatin and liposomal simvastatin treatment. Additionally, SKBR3 has a notably high expression level of human epidermal growth factor receptor 2 (HER2), which we used as a target for our immunoliposomes. To do so we attached humanized anti-HER2 antibody to the envelope of liposomes. We tested the stability and selectivity of the proposed formulation along with the toxicity, ability to induce apoptosis and the effect on signalling pathways involving Akt and Erk kinases. The immunoliposomal formulation of simvastatin is characterized by long-term stability, high selectivity towards HER2-overexpressing breast cancer cells, low non-specific cytotoxicity and effective inhibition of the growth of target cells, presumably by inhibition of signalling pathways and induction of apoptosis. Hence, for the first time, we propose the use of immunoliposomes with simvastatin, targeted directly towards breast cancer cells overexpressing HER2. The prepared immunoliposomes may become a proof of concept in developing new anticancer therapy.

N-hexane Extract and Fraction of Green Tea as Antiproliferation of MCM-B2 Breast Cancer Cells In Vitro

2020 ◽  
Vol 6 (2) ◽  
Author(s):  
Lisni Noraida Waruwu ◽  
Maria Bintang ◽  
Bambang Pontjo Priosoeryanto
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Green Tea ◽  
Cancer Cell ◽  
Breast Cancer Cells ◽  
Green Tea Extract ◽  
Hexane Fraction ◽  
Phytochemical Screening ◽  
Tea Extract

Green tea (Camellia sinensis) is one of traditional plants that have the potential as an anticancer. The sample used in this research commercial green tea extract. The purpose of this study was to test the antiproliferation activity of green tea extract on breast cancer cell MCM-B2 in vitro. Green tea extract fractionated using three solvents, ie water, ethanol 70%, and n-hexane. Extract and fraction of green tea water have value Lethality Concentration 50 (LC50) more than 1000 ppm. The fraction of ethanol 70% and n-hexane had an LC50 value of 883.48 ppm and 600.56 ppm, respectively. The results of the phytochemical screening of green tea extract are flavonoids, tannins, and saponins, while the phytochemical screening results of n-hexane fraction are flavonoids and tannins. Antiproliferation activity was tested on breast cancer cells MCM-B2 and normal cells Vero by trypan blue staining method. The highest MCM-B2 cell inhibitory activity was achieved at a concentration of 13000 ppm green tea extract and 1000 ppm of n-hexane fraction, 59% and 59%, respectively. The extract and n-hexane fraction of green tea are not toxic to normal Vero cells characterized by not inhibiting normal cell proliferation. Keywords: antiproliferative, cancer cell MCM-B2, commercial green tea, cytotoxicity

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