scholarly journals Targeting Cellular Metabolism Chemosensitizes the Doxorubicin-Resistant Human Breast Adenocarcinoma Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Shulan Ma ◽  
Rongfei Jia ◽  
Dongju Li ◽  
Bo Shen

Metabolic energy preferentially produced by glycolysis was an advantageous metabolic phenotype of cancer cells. It is also an essential contributor to the progression of multidrug resistance in cancer cells. By developing human breast cancer MCF-7 cells resistant to doxorubicin (DOX) (MCF-7/MDR cells), the effects and mechanisms of 2-deoxy-D-glucose (2DG), a glucose analogue, on reversing multidrug resistance were investigated. 2DG significantly inhibited the viability of MCF-7/MDR cells and enhanced DOX-induced apoptosis by upregulating protein expression of AMPKα, P53, and caspase-3. The study demonstrated that energy restriction induced by 2DG was relevant to the synergistic effect of 2DG and DOX. The proteins of multidrug gene (the MDR-related protein, MRP1) and P-glycoprotein (P-gp) in MCF-7/MDR cells were downregulated after exposure to 2DG, accompanied with the suppression of the activity of ATP-dependent drug-efflux pump and transmembrane transporter, increasing the intracellular accumulation of DOX to reverse the chemoresistance in multidrug cancer cells.

2011 ◽  
Vol 14 (1) ◽  
pp. 8 ◽  
Author(s):  
Eun-Mi Noh ◽  
Mi Suk Yi ◽  
Hyun Jo Youn ◽  
Byoung Kil Lee ◽  
Young-Rae Lee ◽  
...  

2016 ◽  
Vol 19 (1) ◽  
pp. 45 ◽  
Author(s):  
Masoud Maleki Zadeh ◽  
Nasrin Motamed ◽  
Najmeh Ranji ◽  
Mohammad Majidi ◽  
Fahimeh Falahi

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Mayson H. Alkhatib ◽  
Raghdah S. Bawadud ◽  
Hana M. Gashlan

Abstract Combining more than one anticancer agent in a nanocarrier is beneficial in producing a formula with a low dose and limited adverse side effects. The current study aimed to formulate docetaxel (DTX) and thymoquinone (TQ) in borage oil-based nanoemulsion (B-NE) and evaluate its potential in impeding the growth of breast cancer cells. The formulated B-NE and the combination (DTX + TQ) B-NE were prepared by the ultra-sonication method and physically characterized by the dynamic light scattering techniques. The cytotoxicity analyses of (DTX + TQ) B-NE in MCF-7 and MDA-MB-231 cells were evaluated in vitro by using the SRB assay. Cell death mechanisms were investigated in terms of apoptosis and autophagy pathways by flow cytometry. The optimum mean droplet sizes formulated for blank B-NE and the (DTX + TQ) B-NE were 56.04 ± 4.00 nm and 235.00 ± 10.00 nm, respectively. The determined values of the half-maximal inhibitory concentration (IC50) of mixing one-half amounts of DTX and TQ in B-NE were 1.15 ± 0.097 µM and 0.47 ± 0.091 µM in MCF-7 and MDA-MB-231 cells, respectively, which were similar to the IC50 values of the full amount of free DTX in both tested cell lines. The treatment with (DTX + TQ) B-NE resulted in a synergistic effect on both tested cells. (DTX + TQ) B-NE induced apoptosis that was integrated with the stimulation of autophagy. The produced formulation enhances the DTX efficacy against human breast cancer cells by reducing its effective dose, and thus it could have the potential to minimize the associated toxicity.


2016 ◽  
Vol 38 (2) ◽  
pp. 277-289 ◽  
Author(s):  
Nan Zheng ◽  
Lu Liu ◽  
Wei-wei Liu ◽  
Fei Li ◽  
Toshihiko Hayashi ◽  
...  

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