scholarly journals Diltiazem potentiation of doxorubicin cytotoxicity and cellular uptake in human breast cancer cells

2019 ◽  
Vol 8 (4) ◽  
pp. BMT31
Author(s):  
Hamdan S Al-malky ◽  
Zoheir A Damanhouri ◽  
Jumana Y Al Aama ◽  
Ali A Al Qahtani ◽  
Wafaa S Ramadan ◽  
...  

Aim: Breast cancer is the most common cancer among Arab women and also around the world. Chronic cardiotoxicity and multidrug resistance are potential limiting factors of doxorubicin (DOX), a known anthracycline antibiotic. Materials & methods: DOX cytotoxicity was evaluated by the sulforhodamine method. DOX cellular uptake, detection of P-glycoprotein activity and the photomicrograph of MCF-7 cells were also determined. Results: Diltiazem (DIL) treatment improved DOX cytotoxic activity and increased the cellular uptake of DOX significantly and aggregation of rhodamine 123, reflecting inhibition of P-glycoprotein pump. Cytopathological investigation of MCF-7 cells revealed marked cytotoxic activity of DOX in the presence of DIL. Conclusion: DIL treatment enhanced DOX cytotoxic effect and reduced multidrug resistance, which increased the drug accumulation intracellularly.

2016 ◽  
Vol 13 (6) ◽  
pp. 4745-4750 ◽  
Author(s):  
JINGRU JIANG ◽  
XIAOHONG WANG ◽  
KAI CHENG ◽  
WANZHONG ZHAO ◽  
YITONG HUA ◽  
...  

2012 ◽  
Vol 2012 ◽  
pp. 1-8
Author(s):  
Ping Chen ◽  
Feng Zhang ◽  
Lei Zhang ◽  
Song-Cheng Mao ◽  
Lie Lin ◽  
...  

The kinetics of photosensitizer 2-devinyl-2-(1-methoxylethyl) chlorinf(CPD4) uptake in MCF-7 human breast cancer cells is described by a diffusion kinetics model and experimentally investigated using laser scanning confocal microscopy (LSCM). CPD4 permeated into MCF-7 cells with increasing incubation time, which was followed by its binding to cell organelles. Subcellular distribution study revealed that CPD4 was primarily localized on the mitochondria and membranes, supporting that the mode of transmembrane transport was diffusion. A kinetics model describing CPD4 passing through the plasma membrane of MCF-7 cells was proposed based on Fick's first law of diffusion. The kinetics of cellular uptake of CPD4 was studied by three-dimensional LSCM. By fitting the experimental data using the above model, important cellular uptake and distribution parameters were obtained, which are of clinical significance in photodynamic therapy.


1992 ◽  
Vol 84 (19) ◽  
pp. 1506-1512 ◽  
Author(s):  
R. Clarke ◽  
S. Currier ◽  
O. Kaplan ◽  
E. Lovelace ◽  
V. Boulay ◽  
...  

Author(s):  
Sameer E. Al-harthy ◽  
Mashael S. Al-Motairi ◽  
Huda M. Al-Kreathy ◽  
Fatemah O. Kamel ◽  
Mohamed M. Sayed-Ahmed ◽  
...  

Background: Worldwide, breast cancer is a main cause of morbidity and mortality in females. Doxorubicin (DOX) is an anthracycline anticancer drug and most commonly employed in polychemotherapy protocols in the treatment of solid and hematological tumors. Unfortunately, its optimal clinical benefit is limited secondary to the rapid development of DOX resistance and therapeutic failure. Aim: Therefore, the current study has been initiated to investigate the possible mechanisms whereby the calcium channel blocker Verapamil (VER) could decrease DOX resistance and enhance the cytotoxic activity of DOX against the growth of human breast cancer cells. Methodology: To achieve the ultimate goal of this study, we have examined DOX-induced cytotoxicity, apoptosis, alteration in the function of multidrug resistance proteins and cell cycle phase distribution against MCF-7 cell line in presence and absence of Verapamil.  Results: Addition of VER enhanced the cytotoxic effect of DOX against the growth of MCF-7 cells which manifested as a significant decrease in the IC50 from 36 µg/ml for DOX alone to 13 µg/ml for DOX plus VER.  Moreover, combined treatment with VER and DOX significantly increased percentage of early apoptosis and cells arrested in G0/G1 phase when compared to DOX alone. In addition, VER significantly increased DOX cellular uptake through inhibition of the function of multidrug resistant proteins.   Conclusion: VER treatment enhanced the cytotoxic activity of DOX against the growth of MCF-7 cells secondary to increase its cellular accumulation.  The observed increase in DOX uptake by VER was parallel to increased accumulation of Rho-123 dye which my point to the contribution of inhibition of multidrug resistant proteins by VER in the enhancement of DOX cytotoxicity.


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