Gemcitabine: A Critical Nucleoside for Cancer Therapy

Gesto, Diana; Cerqueira, Nuno M. F. S. A.; Fernandes, P.; Ramos, María J.

doi:10.2174/092986712799320682

Cited by 90 publications

(75 citation statements)

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“…104,105 RRs catalyze the conversion of nucleoside 5′-diphosphates (ie, NDPs) to their corresponding deoxynucleotides (ie, dNDPs), which are phosphorylated to dNTPs for DNA synthesis. 105,106 Inhibition of RRs will reduce the dNTP pool, allowing dFdCTP to more effectively compete with dNTPs and inhibit DNA replication and repair.…”

Section: Gemcitabine and Its Mechanisms Of Actionmentioning

confidence: 99%

Overcoming tumor cell chemoresistance using nanoparticles: lysosomes are beneficial for (stearoyl) gemcitabine-incorporated solid lipid nanoparticles

Chen¹,

Zheng²,

Shi³

et al. 2018

IJN

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Despite recent advances in targeted therapies and immunotherapies, chemotherapy using cytotoxic agents remains an indispensable modality in cancer treatment. Recently, there has been a growing emphasis in using nanomedicine in cancer chemotherapy, and several nanomedicines have already been used clinically to treat cancers. There is evidence that formulating small molecular cancer chemotherapeutic agents into nanomedicines significantly modifies their pharmacokinetics and often improves their efficacy. Importantly, cancer cells often develop resistance to chemotherapy, and formulating anticancer drugs into nanomedicines also helps overcome chemoresistance. In this review, we briefly describe the different classes of cancer chemotherapeutic agents, their mechanisms of action and resistance, and evidence of overcoming the resistance using nanomedicines. We then emphasize on gemcitabine and our experience in discovering the unique (stearoyl) gemcitabine solid lipid nanoparticles that are effective against tumor cells resistant to gemcitabine and elucidate the underlying mechanisms. It seems that lysosomes, which are an obstacle in the delivery of many drugs, are actually beneficial for our (stearoyl) gemcitabine solid lipid nanoparticles to overcome tumor cell resistance to gemcitabine.

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Section: Gemcitabine and Its Mechanisms Of Actionmentioning

confidence: 99%

Overcoming tumor cell chemoresistance using nanoparticles: lysosomes are beneficial for (stearoyl) gemcitabine-incorporated solid lipid nanoparticles

Chen¹,

Zheng²,

Shi³

et al. 2018

IJN

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“…hENT4, also known as PMAT, is uniquely selective for adenosine and also transports a variety of organic cations [16][17][18][19][20]. Some nucleosidederived drugs can also interact with and be translocated by members of the SLC22 gene family, which include organic anion transporters (OATs), organic cation transporters (OCTs) and organic carnitine and zwitterion transporters (OCTNs) [9,[21][22][23][24][25].…”

Section: Review Articlementioning

confidence: 99%

Nucleoside transporters in PET imaging of proliferating cancer cells using 3ꞌ-deoxy-3ꞌ-[18F]fluoro-L-thymidine

Saidijam¹,

Afshar²,

Ahmad³

et al. 2018

J Diagn Imaging Ther

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The movement of physiologic nucleosides and nucleoside analogue drugs across biological membranes is mediated by nucleoside transport proteins. In cancer, nucleoside transporters have an important role in maintaining the hyperproliferative state of tumours and are important targets for diagnostic and therapeutic agents in the detection, treatment and monitoring of cancers. The nucleoside-based probe 3ꞌ-deoxy-3ꞌ-

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“…Tamoxifen is another fluorinated compound used for treatment of hormonedependent breast cancer as an oestrogen antagonist 16 . Gemcitabine is another fluorinated compound used in the treatment of some cancers 17 . In the present study our aim is to determine the antiproliferative properties of fluorinated Schiff bases on a K562 myelomonocytic leukemic cell line using a CFSE assay, which could provide considerable quantitative data.…”

mentioning

confidence: 99%

Antiproliferative Effects of Fluorine Substitute 3,5-di-<i>tert</i>-butylphenol Bearing Schiff Bases Using CFSE-Based Cell Proliferation Assay

Gürol¹,

Kasim²,

Süzergöz³

2017

Current Science

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The determination of antiproliferative properties of compounds on tumour cells is important for assessment of their efficacy in cancer treatment. CFSElabelled K562 cells were incubated with doxorubicin and ortho-or para-fluorosubstitute Schiff bases (compounds 1 and 2 respectively). CFSE intensities were analysed using flow cytometry. K562 cells treated with doxorubicin resulted in homogeneous high intensity fluorescence after 96 h of incubation. Schiff bases exhibited antiproliferative effects, but lower than doxorubicin. Our results reveal that CFSE assay can be used for determining in vitro antiproliferative features of anticancer drugs and/or compounds from herbal or chemical sources.Keywords: Cancer, CFSE, doxorubicin.THERE have been many attempts to explore new chemotherapeutic agents from chemical and herbal sources worldwide. The determination of cytotoxic and antiproliferative effects of organic compounds has crucial importance in the evaluation of anticancer potential 1 . Although there are some precise methods such as 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) or ATP-based tumour chemosensitivity (ATP-TCA) assays to determine the cytotoxic capacity of herbal or chemical compounds [2][3][4] , there are no precise methods to quantitively determine the antiproliferative effects of compounds or assess multiparameters in anticancer research.The carboxyfluorescein diacetate succinimidyl ester (CFSE) assay is currently used to determine cell proliferation with flow cytometry 5 . The CFSE assay is based on general protein labelling by CFSE in which an aminoreactive dye forms stable covalent bonds with cell proteins [6][7][8] . An equal and progressive division of CFSE fluorescence occurs within daughter cells after each cellular division which suggests in vitro cell proliferation 9 . This fluorescent cell tracking assay can be a powerful tool to study the antiproliferative effects of anticancer drugs or herbal and chemical compounds in vitro.Schiff bases derived from an amine and carboxylic compounds belong to a class of ligands involved in the coordination of metal ions via azomethine nitrogen 10 . The C=N linkage is crucial for biological activity in azomethine derivatives, and it was reported that various azomethines are characterized to have roles against bacteria, fungi and cancer11 . An appreciable amount of Schiff-base complexes are quite successful models of biological compounds 12 . Fluorinated compounds have recently drawn attention due to their therapeutic applications in various medical areas 13 . 5-Fluorouracil (5-FU), a synthetic flourinated antineoplastic agent, is being used as an antimetabolite to treat malignancies such as breast, head, neck and gastrointestinal malignancies 14 . 5-FU irreversibly inhibiting thymidylate synthase can cause the death of rapidly dividing cancerous cells 15 . Tamoxifen is another fluorinated compound used for treatment of hormonedependent breast cancer as an oestrogen antagonist 16 . Gemcitabine is another fluorinated compound used in the...

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Gemcitabine: A Critical Nucleoside for Cancer Therapy

Cited by 90 publications

References 0 publications

Overcoming tumor cell chemoresistance using nanoparticles: lysosomes are beneficial for (stearoyl) gemcitabine-incorporated solid lipid nanoparticles

Overcoming tumor cell chemoresistance using nanoparticles: lysosomes are beneficial for (stearoyl) gemcitabine-incorporated solid lipid nanoparticles

Nucleoside transporters in PET imaging of proliferating cancer cells using 3ꞌ-deoxy-3ꞌ-[18F]fluoro-L-thymidine

Antiproliferative Effects of Fluorine Substitute 3,5-di-<i>tert</i>-butylphenol Bearing Schiff Bases Using CFSE-Based Cell Proliferation Assay

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