scholarly journals Cytotoxic Effect of Paclitaxel and Lapatinib Co-Delivered in Polylactide-co-Poly(ethylene glycol) Micelles on HER-2-Negative Breast Cancer Cells

Pharmaceutics ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 169 ◽  
Author(s):  
Alicja Zajdel ◽  
Adam Wilczok ◽  
Katarzyna Jelonek ◽  
Monika Musiał-Kulik ◽  
Aleksander Foryś ◽  
...  

To find better strategies to enhance the cytotoxic effect of paclitaxel (PTX) and lapatinib (LAP) against breast cancer cells, we analyzed the efficacy of a novel delivery system containing polylactide-co-poly(ethylene glycol) (PLA-PEG) filomicelles of over 100 nm in length and spherical micelles of approximately 20 nm in diameter. The 1H NMR measurements confirmed the incorporation of PTX and LAP into micelles. Analysis of the drug release mechanism revealed the diffusion-controlled release of LAP and anomalous transport of PTX. Drug content analysis in lyophilized micelles and micellar solution showed their good storage stability for at least 6 weeks. Blank micelles, LAP-loaded micelles and free LAP did not affect MCF-7 breast cancer cell proliferation, suggesting that the cytotoxicity of PTX-, PTX/LAP-loaded micelles, and the binary mixture of free PTX and LAP was solely caused by PTX. PTX/LAP-loaded micelles showed greater toxicity compared to the binary mixture of PTX and LAP after 48 h and 72 h. Only free PTX alone induced P-gp activity. This study showed the feasibility of using a LAP and PTX combination to overcome MDR in MCF-7 cells, particularly when co-loaded into micelles. We suggest that PTX/LAP micelles can be applicable not only for the therapy of HER-2-positive, but also HER-2-negative breast cancers.

2019 ◽  
Vol 43 (1) ◽  
pp. 238-248 ◽  
Author(s):  
Roya Binaymotlagh ◽  
Farid Hajareh Haghighi ◽  
Fatemeh Aboutalebi ◽  
Seyede Zohreh Mirahmadi-Zare ◽  
Hassan Hadadzadeh ◽  
...  

The combination of diagnosis and targeted therapy within a single nanoplatform is one of the remarkable advances in molecular medicine.


2017 ◽  
Vol 80 ◽  
pp. 301-312 ◽  
Author(s):  
Parvin Mahdaviani ◽  
Saeed Bahadorikhalili ◽  
Mona Navaei-Nigjeh ◽  
Seyed Yaser Vafaei ◽  
Mehdi Esfandyari-Manesh ◽  
...  

2018 ◽  
Vol Volume 11 ◽  
pp. 7669-7677 ◽  
Author(s):  
Maryam Hamzeloo-Moghadam ◽  
Mahmoud Aghaei ◽  
Mohammad Hossein Abdolmohammadi ◽  
Amir Khalaj ◽  
Faranak Fallahian

Steroids ◽  
2020 ◽  
Vol 160 ◽  
pp. 108656 ◽  
Author(s):  
Ahmed Ismail ◽  
Ahmed S. Doghish ◽  
Bakheet E. M. Elsadek ◽  
Salama A. Salama ◽  
Amr D. Mariee

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13100-13100
Author(s):  
L. Witters ◽  
A. Witkoski ◽  
M. Planas-Silva ◽  
J. Viallet ◽  
M. S. Berger ◽  
...  

13100 Background: The epidermal growth factor receptor (EGFR; ErbB1) and HER-2/neu (ErbB2), members of the ErbB family of receptor tyrosine kinases, are overexpressed in a variety of human tumors and overexpression generally correlates with poor prognosis and decreased survival. Use of inhibitors of these receptors as monotherapies, e.g., trastuzumab, Iressa, and erlotinib, has led to advances in treatment, but many patients do not respond or develop resistance. The anti-apoptotic protein, Bcl-2, is also overexpressed in a number of human tumors. Inhibitors of Bcl-2 induce apoptosis and sensitize cancer cells to other therapies. This study assesses the effects of a combination of a reversible inhibitor of both EGFR and HER-2/neu that is similar to lapatinib (GW2974) and a pan inhibitor of the Bcl-2 family (GX15–070: Gemin X Biotechnologies, Inc.) on the growth of human breast cancer cells. Methods: The MCF-7 human breast cancer cell line transfected with a control vector, MCF/neo, and the HER-2/neu transfected MCF-7 cell line, MCF/18, were treated with various concentrations of GW2974 (0.25–10 μM) and/or the GX15–070 pan Bcl-2 inhibitor (50–500 nM). After a 3 day exposure, cell number was determined using the colorimetric MTT tetrazolium dye assay. Percent of control was normalized to corresponding concentrations of the solvent for both agents (DMSO). Results: Treatment with the GW2974 dual inhibitor or the GX15–070 pan Bcl-2 inhibitor resulted in dose-dependent growth inhibition in both the control and HER-2/neu transfected MCF-7 cell lines. The combination of both agents produced synergistic growth inhibition in both cell lines as confirmed by isobologram analysis. Conclusions: This study has demonstrated synergy with the combination of a dual inhibitor of EGFR and HER-2/neu and an inhibitor of Bcl-2 in control and HER-2/neu overexpressing MCF-7 human breast cancer cells. This finding warrants an evaluation of this combination in clinical trials for the treatment of patients with metastatic breast cancer. [Table: see text]


2021 ◽  
Vol 3 (2) ◽  
pp. 72-80
Author(s):  
Dita Sozianty ◽  
Rifki Febriansah

Background: Breast cancers occur because of an impaired balance between proliferation, differentiation, and apoptosis of breast glands. Natural products have potency as cytotoxic agents with less side effects than chemotherapy. One of the potential plants is Anredera cordifolia (Ten.) Stennis (binahong), which contains flavonoid 8-glucopyranosyl- 4’,5,7-trihydroxy flavone compounds.Objective: This study aims to determine the potency of binahong leaves extract as an anticancer for breast cancer in vitro and in silico.Methods: Preliminary tests using molecular docking of 8-glucopyranosyl-4’,5,7-trihydroxyflavone compounds on Bcl-2 and HER-2 proteins. The extraction and fractionation were to obtain binahong extract. Thin layer chromatography to identify flavonoid compounds in the extract. DPPH assay was performed to evaluate the antioxidant activity. MTT assay was performed to evaluate cytotoxic activity on MCF-7 breast cancer cells and Vero cells.Results: In silico test showed a stable bond between 8-glucopyranosyl- 4’,5,7-trihydroxylflavone, and Bcl-2 and HER-2 with a docking score of -7.5 kcal/mol and -8.0 kcal/mol, respectively. The binahong extract contain flavonoid compounds that had the retention factor value 0.78; 0.49; 0.35. Antioxidant test resulted IC50 value of 4940 μg/mL. Cytotoxic test resulted in IC50 value of 1073 μg/mL and 486 μg/mL for Vero cells and MCF-7 breast cancer cells, respectively. The comparison between IC50 produced a selectivity index value of 2.149, which shows that binahong extract was selective against MCF-7 breast cancers.Conclusion: This study concluded that binahong extract has weak potency as anticancer agent on MCF-7 cells.


2021 ◽  
Vol 22 (17) ◽  
pp. 9511
Author(s):  
Dominika Komorowska ◽  
Agnieszka Gajewska ◽  
Paweł Hikisz ◽  
Grzegorz Bartosz ◽  
Aleksandra Rodacka

Radiotherapy is among the most important methods for breast cancer treatment. However, this method’s effectiveness is limited by radioresistance. The aim of this study was to investigate whether the stilbene derivatives piceid, resveratrol, and piceatannol have a radiosensitising effect on breast cancer cells (MCF-7). The conducted research enabled us to determine which of the tested compounds has the greatest potential in sensitising cells to ionising radiation (IR). Among the stilbene derivatives, resveratrol significantly increased the effect of IR. Resveratrol and IR used in combination had a higher cytotoxic effect on MCF-7 cells than using piceatannol, piceid, or radiation alone. This was due to a significant decrease in the activity of antioxidant enzymes, which resulted in the accumulation of formed reactive oxygen species (ROS). The effect of resveratrol and IR enhanced the expression of apoptotic genes, such as Bax, p53, and caspase 8, leading to apoptosis.


Sign in / Sign up

Export Citation Format

Share Document