Targeted delivery of doxorubicin through CD44 aptamer to cancer cells

2021 ◽  
Author(s):  
Jagadish Natesh ◽  
Chetan Chandola ◽  
Syed Musthapa Meeran ◽  
Muniasamy Neerathilingam

Aim: The current investigation is focused on the targeted delivery of doxorubicin through CD44-aptamer-mediated active targeting to the human breast cancer cells. Methods: CD44-aptamer-doxorubicin (Apt-Dox) conjugates were developed by incubating different molar ratios of aptamer and doxorubicin. Cytotoxicity, selective intracellular accumulation and uptake of the Apt–Dox conjugates were analyzed to evaluate the efficacy of Apt–Dox conjugates. Results: Dox was efficiently conjugated with aptamer at 1:2 Apt–Dox molar ratios. Apt–Dox conjugate significantly inhibited the proliferation of CD44-overexpressing breast cancer cells, whereas negligible inhibition of cell proliferation was found in the control cells. Apt–Dox conjugate selectively internalized and accumulated in CD44-overexpressing cells. Conclusion: Apt–Dox conjugate selectively delivers doxorubicin to CD44-expressing cancer cells, thereby inhibiting selective cell proliferation and enhancing the targeted therapy.

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Meng-Wong Taing ◽  
Jean-Thomas Pierson ◽  
Paul N. Shaw ◽  
Ralf G. Dietzgen ◽  
Sarah J. Roberts-Thomson ◽  
...  

The assessment of human cancer cell proliferation is a common approach in identifying plant extracts that have potential bioactive effects. In this study, we tested the hypothesis that methanolic extracts of peel and flesh from three archetypal mango cultivars, Irwin (IW), Nam Doc Mai (NDM), and Kensington Pride (KP), differentially affect proliferation, extracellular signal-regulated kinase (ERK) activity, and intracellular calcium ([Ca2+]I) signalling in MCF-7 human breast cancer cells. Mango flesh extracts from all three cultivars did not inhibit cell growth, and of the peel extracts only NDM reduced MCF-7 cell proliferation. Mango cultivar peel and flesh extracts did not significantly change ERK phosphorylation compared to controls; however, some reduced relative maximal peak[Ca2+]Iafter adenosine triphosphate stimulation, with NDM peel extract having the greatest effect among the treatments. Our results identify mango interfruit and intrafruit (peel and flesh) extract variability in antiproliferative effects and[Ca2+]Isignalling in MCF-7 breast cancer cells and highlight that parts of the fruit (such as peel and flesh) and cultivar differences are important factors to consider when assessing potential chemopreventive bioactive compounds in plants extracts.


2010 ◽  
Vol 316 (3) ◽  
pp. 433-442 ◽  
Author(s):  
Rocío García-Becerra ◽  
Lorenza Díaz ◽  
Javier Camacho ◽  
David Barrera ◽  
David Ordaz-Rosado ◽  
...  

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 628
Author(s):  
Jilei Zhang ◽  
Rong Lu ◽  
Yongguo Zhang ◽  
Żaneta Matuszek ◽  
Wen Zhang ◽  
...  

Background: Transfer RNA (tRNA) queuosine (Q)-modifications occur specifically in 4 cellular tRNAs at the wobble anticodon position. tRNA Q-modification in human cells depends on the gut microbiome because the microbiome product queuine is required for its installation by the enzyme Q tRNA ribosyltransferase catalytic subunit 1 (QTRT1) encoded in the human genome. Queuine is a micronutrient from diet and microbiome. Although tRNA Q-modification has been studied for a long time regarding its properties in decoding and tRNA fragment generation, how QTRT1 affects tumorigenesis and the microbiome is still poorly understood. Results: We generated single clones of QTRT1-knockout breast cancer MCF7 cells using Double Nickase Plasmid. We also established a QTRT1-knockdown breast MDA-MB-231 cell line. The impacts of QTRT1 deletion or reduction on cell proliferation and migration in vitro were evaluated using cell culture, while the regulations on tumor growth in vivo were evaluated using a xenograft BALB/c nude mouse model. We found that QTRT1 deficiency in human breast cancer cells could change the functions of regulation genes, which are critical in cell proliferation, tight junction formation, and migration in human breast cancer cells in vitro and a breast tumor mouse model in vivo. We identified that several core bacteria, such as Lachnospiraceae, Lactobacillus, and Alistipes, were markedly changed in mice post injection with breast cancer cells. The relative abundance of bacteria in tumors induced from wildtype cells was significantly higher than those of QTRT1 deficiency cells. Conclusions: Our results demonstrate that the QTRT1 gene and tRNA Q-modification altered cell proliferation, junctions, and microbiome in tumors and the intestine, thus playing a critical role in breast cancer development.


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