New combination strategy of doxorubicin and epoxomicin in biocompatibility: Biodegradable polymeric nanoparticles increase apoptosis in breast cancer cells

2017 ◽  
Vol 256 ◽  
pp. S36
Author(s):  
Ertan Kucuksayan ◽  
Fatih Bozkurt ◽  
Tomris Ozben ◽  
Perihan Kubra Cicek ◽  
Aysegul Hanikoglu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Polymeric Nanoparticles ◽  
New Combination ◽  
Combination Strategy

Abstract 16201: Combined Treatment of the PI3k/mTOR Inhibitor BEZ235 With Doxorubicin Does Not Increase Cardiotoxicity While Improving Efficacy in Breast Cancer Cells

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
David E Durrant ◽  
Samya Dyer ◽  
Anindita Das ◽  
Rakesh C Kukreja
Keyword(s):  
Breast Cancer ◽  
Ejection Fraction ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Mtor Inhibitor ◽  
Systolic Function ◽  
Combined Treatment ◽  
Combination Group ◽  
Individual Treatment ◽  
Combination Strategy

Background: Cardiotoxicity is a major clinical limitation with doxorubicin (DOX). Also, the PI3K/Akt survival pathway is one of the most commonly mutated pathways in cancer. Therefore, the combination of kinase inhibitors and chemotherapy, such as DOX, are necessary for achieving cancer control. The PI3K pathway is also critical for protecting the heart from stress. Therefore, we examined the combined effect of BEZ235 (BEZ), a dual PI3k/mTOR inhibitor, with DOX on cardiac function and killing of breast cancer cells. Methods and results: c57 mice were treated with BEZ (40 mg/kg daily oral gavage) and DOX (3 IV injections of 5 mg/kg) either alone or in combination. Systolic function was assessed 12 weeks after initial treatment using echocardiography. Decreased ejection fraction was observed after DOX treatment. Interestingly, the combined treatment with BEZ and DOX did not exacerbate DOX cardiotoxicity (Fig. A). Western blot analysis showed significant increase in AKT (thr 308) and ERK phosphorylation with BEZ and DOX as compared individual treatment with BEZ or DOX in the heart (Fig. B). To address the anti-cancer effects of these drugs, MDA-MB-231 breast cancer cells were treated with BEZ and DOX either alone or in combination for 48 hours. Necrosis, measured using the trypan blue assay, showed a significant increase in dead cells compared to either drug alone (Fig. C). Conclusion: Concurrent treatment with DOX and BEZ did not exacerbate cardiac toxicity as demonstrated by similar level of deficit in ejection fraction between DOX as well as DOX plus BEZ. This could be due to enhanced survival signaling in the combination group. BEZ also sensitized breast cancer cells to DOX resulting in increased cell death. We propose that this combination strategy might lead to improved long term outcomes for patients with breast cancer without additional complications related to cardiac dysfunction.

scholarly journals Electrospray-based synthesis of fluorescent poly(d,l-lactide-co-glycolide) nanoparticles for the efficient delivery of an anticancer drug and self-monitoring its effect in drug-resistant breast cancer cells

2020 ◽  
Vol 1 (8) ◽  
pp. 3033-3048
Author(s):  
Manosree Chatterjee ◽  
Ritwik Maity ◽  
Souvik Das ◽  
Nibedita Mahata ◽  
Biswarup Basu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Polymeric Nanoparticles ◽  
Metastatic Breast ◽  
Drug Resistant ◽  
Blue Fluorescence ◽  
Self Monitoring ◽  
Novel Approach ◽  
Efficient Delivery

A novel approach used to synthesize antimetabolite-conjugated and intense blue fluorescence-emitting smart polymeric nanoparticles is reported for the efficient delivery of anticancer drugs and self-monitoring their effect in drug-resistant metastatic breast cancer cells.

Thermosensitive folic acid-targeted poly (ethylene-co-vinyl alcohol) hemisuccinate polymeric nanoparticles for delivery of epirubicin to breast cancer cells

2016 ◽  
Vol 25 (11) ◽  
pp. 967-976 ◽  
Author(s):  
Farshid Hassanzadeh ◽  
Sahar Maaleki ◽  
Jaleh Varshosaz ◽  
Ghadam Ali Khodarahmi ◽  
Maryam Farzan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Folic Acid ◽  
Cancer Cells ◽  
Vinyl Alcohol ◽  
Breast Cancer Cells ◽  
Polymeric Nanoparticles ◽  
Poly Ethylene

scholarly journals A new combination strategy to enhance apoptosis in cancer cells by using nanoparticles as biocompatible drug delivery carriers

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ertan Kucuksayan ◽  
Fatih Bozkurt ◽  
Mustafa Tahsin Yilmaz ◽  
Aslinur Sircan-Kucuksayan ◽  
Aysegul Hanikoglu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Delivery ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Clinical Studies ◽  
Encapsulation Efficiency ◽  
In Vitro Release ◽  
New Combination ◽  
Combination Strategy ◽  
Normal Cells

AbstractSome experimental and clinical studies have been conducted for the usage of chemotherapeutic drugs encapsulated into nanoparticles (NPs). However, no study has been conducted so far on the co-encapsulation of doxorubicin (Dox) and epoxomicin (Epo) into NPs as biocompatible drug delivery carriers. Therefore, we investigated if co-encapsulation of doxorubicin (Dox) and/or epoxomicin (Epo) into NPs enhance their anticancer efficiency and prevent drug resistance and toxicity to normal cells. We synthesized Dox and/or Epo loaded poly (lactic-co-glycolic acid) (PLGA) NPs using a multiple emulsion solvent evaporation technique and characterized them in terms of their particle size and stability, surface, molecular, thermal, encapsulation efficiency and in vitro release properties. We studied the effects of drug encapsulated NPs on cellular accumulation, intracellular drug levels, oxidative stress status, cellular viability, drug resistance, 20S proteasome activity, cytosolic Nuclear Factor Kappa B (NF-κB-p65), and apoptosis in breast cancer and normal cells. Our results proved that the nanoparticles we synthesized were thermally stable possessing higher encapsulation efficiency and particle stability. Thermal, morphological and molecular analyses demonstrated the presence of Dox and/or Epo within NPs, indicating that they were successfully loaded. Cell line assays proved that Dox and Epo loaded NPs were less cytotoxic to single-layer normal HUVECs than free Dox and Epo, suggesting that the NPs would be biocompatible drug delivery carriers. The apoptotic index of free Dox and Epo increased 50% through their encapsulation into NPs, proving combination strategy to enhance apoptosis in breast cancer cells. Our results demonstrated that the co-encapsulation of Dox and Epo within NPs would be a promising treatment strategy to overcome multidrug resistance and toxicity to normal tissues that can be studied in further in vivo and clinical studies in breast cancer.

scholarly journals Dual Inhibition of Ornithine Decarboxylase and A1 Adenosine Receptor Efficiently Suppresses Breast Tumor Cells

2021 ◽  
Vol 11 ◽  
Author(s):  
Hongyan Ma ◽  
Qizhang Li ◽  
Jing Wang ◽  
Jing Pan ◽  
Zhengding Su ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Adenosine Receptor ◽  
Breast Cancer Cells ◽  
New Combination ◽  
Combination Therapies ◽  
Camp Concentration ◽  
Polyamine Synthesis ◽  
Dual Inhibition ◽  
Mcf 7

Personized treatment of breast cancer is still a challenge, and more treatment options for breast cancer are warranted. Combination therapies have been a highly appreciated strategy for breast cancer treatment in recent years, and the development of new combination therapies could improve patient outcomes. Adenosine and polyamines are both endogenous metabolites with indispensable biological functions. Adenosine binds with the A1 adenosine receptor (A1AR) to downregulate cAMP concentration, and both low cAMP content and high polyamine levels stimulate the growth and proliferation of cancer cells. In this work, we initially used a polyamine synthesis inhibitor, DFMO (α-difluoromethylornithine), and an A1AR inhibitor, DPCPX (8-cyclopentyl-1,3-dipropylxanthine) to investigate if simultaneously inhibiting A1AR and polyamine synthesis has synergistical antitumor effects. Next, we investigated a dual inhibitor (ODC-MPI-2) of A1AR and ODC (ornithine decarboxylase 1), the rate-limiting enzyme in polyamine biosynthesis. We investigated if ODC-MPI-2 could inhibit the proliferation and growth of breast cancer cells. Our data showed that DFMO and DPCPX synergistically inhibit the growth and proliferation of MCF-7 cells. We also demonstrated that ODC-MPI-2 reduces cellular polyamine levels and elevates cAMP concentration. We further showed that ODC-MPI-2 inhibits the growth, proliferation, and migration/invasion of MCF-7 cells. Finally, ODC-MPI-2 showed a preference for inhibiting triple-negative breast cancer cells. The dual inhibition of ODC and A1AR is a new combination therapy strategy for treating breast cancer, and dual inhibitors of ODC and A1AR may be effective future drugs for treating breast cancer.

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