Overcoming Taxane and Anthracycline Resistance

Zelnak, Amelia

doi:10.1111/j.1524-4741.2010.00911.x

Cited by 27 publications

(38 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Typical taxanes used in current treatment regimens for breast cancer include paclitaxel (Taxol) and docetaxel (Taxotere), while typical anthracyclines include doxorubicin (Adriamycin) and epirubicin (Pharmorubicin) [4,5]. Docetaxel belongs to the group of taxanes that were first introduced into clinical use during the 1990’s.…”

Section: Introductionmentioning

confidence: 99%

“…ABC transporter substrates include a diverse array of compounds, many of them structurally unrelated. These proteins protect cells and tissues by exporting potential toxins, including anticancer agents from cells in normal tissues and cancer cells [4]. In general, ABCB1 transports large hydrophobic compounds, whereas ABCC1 and ABCG2 transport both hydrophobic drugs and large anionic compounds [15].…”

Section: Introductionmentioning

confidence: 99%

“…In general, ABCB1 transports large hydrophobic compounds, whereas ABCC1 and ABCG2 transport both hydrophobic drugs and large anionic compounds [15]. ABC proteins have been implicated in both taxane and doxorubicin resistance in breast cancers [1,3,4,14]. When 60 cell lines were tested, it was found that the lower the ABCB1 expression level, the greater the sensitivity to paclitaxel in the cell lines [16].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Multiple mechanisms underlying acquired resistance to taxanes in selected docetaxel-resistant MCF-7 breast cancer cells

Wang

Hajar

et al. 2014

BMC Cancer

View full text Add to dashboard Cite

BackgroundChemoresistance is a major factor involved in a poor response and reduced overall survival in patients with advanced breast cancer. Although extensive studies have been carried out to understand the mechanisms of chemoresistance, many questions remain unanswered.MethodsIn this research, we used two isogenic MCF-7 breast cancer cell lines selected for resistance to doxorubicin (MCF-7DOX) or docetaxel (MCF-7TXT) and the wild type parental cell line (MCF-7CC) to study mechanisms underlying acquired resistance to taxanes in MCF-7TXT cells. Cytotoxicity assay, immunoblotting, indirect immunofluorescence and live imaging were used to study the drug resistance, the expression levels of drug transporters and various tubulin isoforms, apoptosis, microtubule formation, and microtubule dynamics.ResultsMCF-7TXT cells were cross resistant to paclitaxel, but not to doxorubicin. MCF-7DOX cells were not cross-resistant to taxanes. We also showed that multiple mechanisms are involved in the resistance to taxanes in MCF-7TXT cells. Firstly, MCF-7TXT cells express higher level of ABCB1. Secondly, the microtubule dynamics of MCF-7TXT cells are weak and insensitive to the docetaxel treatment, which may partially explain why docetaxel is less effective in inducing M-phase arrest and apoptosis in MCF-7TXT cells in comparison with MCF-7CC cells. Moreover, MCF-7TXT cells express relatively higher levels of β2- and β4-tubulin and relatively lower levels of β3-tubulin than both MCF-7CC and MCF-7DOX cells. The subcellular localization of various β-tubulin isoforms in MCF-7TXT cells is also different from that in MCF-7CC and MCF-7DOX cells.ConclusionMultiple mechanisms are involved in the resistance to taxanes in MCF-7TXT cells. The high expression level of ABCB1, the specific composition and localization of β-tubulin isoforms, the weak microtubule dynamics and its insensitivity to docetaxel may all contribute to the acquired resistance of MCF-7TXT cells to taxanes.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Multiple mechanisms underlying acquired resistance to taxanes in selected docetaxel-resistant MCF-7 breast cancer cells

Wang

Hajar

et al. 2014

BMC Cancer

View full text Add to dashboard Cite

show abstract

“…(51) However, drug resistance, as manifested by relapse and cancer progression, still remains a major challenge. Various mechanisms in acquired or secondary taxane resistance have been reported, (52,53) and recent studies demonstrated that some kinesin proteins also play critical roles in taxane resistance. (32,54) In breast cancer, De et al (32) identified KIFC3 as the gene responsible for docetaxel resistance of cancer cells.…”

Section: Involvement Of Kif In Taxane Resistancementioning

confidence: 99%

“…The cause of drug resistance is complicated and the expression of efflux pumps and antiapoptotic proteins might be a major mechanism. (52,53) Some KIF proteins, such as KIFC3 and MCAK, might be involved in drug resistance. (29,32) The strategy of targeting KIF combined with chemotherapy might therefore provide an alternative way to treat cancer when serious chemotherapeutic drug resistance exists.…”

Section: Involvement Of Kif In Taxane Resistancementioning

confidence: 99%

Oncogenic role of kinesin proteins and targeting kinesin therapy

2013

View full text Add to dashboard Cite

The kinesin superfamily (KIF) is a group of proteins that share a highly conserved motor domain. Except for some members, many KIF proteins have adenosine triphosphatase activity and microtubule‐dependent plus‐end motion ability. Kinesins participate in several essential cellular functions, including mitosis, meiosis and the transport of macromolecules. Increasing evidence indicates kinesin proteins play critical roles in the genesis and development of human cancers. Some kinesin proteins are associated with maligancy as well as drug resistance of solid tumor. Thus, targeting KIF therapy seems to be a promising anticancer strategy. Inhibitors of KIF such as kinesin spindle protein (KSP/Eg5) have entered clinical trials for monotherapy or in combination with other drugs, and kinesins other than Eg5 with various potential anticancer target characteristics are also constantly being discovered and studied. Here, we summarize the oncogenic roles of kinesin proteins and potential cancer therapy strategies that target KIF.

show abstract

Concanavalin A induces apoptosis in a dose‐dependent manner by modulating thiol/disulfide homeostasis in C6 glioblastoma cells

Kar

Kaçar

Hacıoğlu

et al. 2021

J Biochem & Molecular Tox

View full text Add to dashboard Cite

Glioma is the most common brain tumor. C6 rat glioblastoma cells provide the possibility to the scientist to study brain cancer. Concanavalin A (Con A) has a lot of antitumoral effects, especially over oxidative stress. In the present study, it was aimed to decide the impacts of various doses of Con A on C6 glioblastoma cells regarding cytotoxicity, thiol/disulfide homeostasis, apoptosis, and inflammation. We detected the cytotoxic activity of Con A (from 7.8 to 500 µg/ml) in C6 cells by utilizing 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT) and determined the toxic concentration of Con A. Once the optimal doses were found, the thiol–disulfide homeostasis, levels of total antioxidant and oxidant status (TAS and TOS), malondialdehyde (MDA) and glutathione (GSH), pro‐inflammatory cytokines as tumor necrosis factor‐alpha (TNF‐α) and interleukin‐6 (IL‐6), apoptotic proteins as cytochrome c (CYCS), and caspase 3 (CASP3) were measured. Apoptotic and morphological changes in the C6 cells were examined with an inverted microscope and flow cytometry technique. Dose‐dependent Con A triggered oxidative damage in the C6 cells, affecting the inflammatory pathway, so reducing proliferation with apoptotic proteins and morphological changes. But especially, Con A increased disulfide formation by disrupting the thiol/disulfide balance in C6 cells. This study revealed that Con A, known as carbohydrate‐binding protein, generated oxidative damage, inflammation, and apoptosis in a dose‐dependent manner by modulating thiol/disulfide homeostasis in C6 glioblastoma cells.

show abstract

Overcoming Taxane and Anthracycline Resistance

Cited by 27 publications

References 30 publications

Multiple mechanisms underlying acquired resistance to taxanes in selected docetaxel-resistant MCF-7 breast cancer cells

Multiple mechanisms underlying acquired resistance to taxanes in selected docetaxel-resistant MCF-7 breast cancer cells

Oncogenic role of kinesin proteins and targeting kinesin therapy

Concanavalin A induces apoptosis in a dose‐dependent manner by modulating thiol/disulfide homeostasis in C6 glioblastoma cells

Contact Info

Product

Resources

About