Function of Aurora kinase A in Taxol-resistant breast cancer and its correlation with P-gp

Li, Yan; Tang, Ke; Zhang, Haijing; Zhang, Yi; Zhou, Wanqi; Chen, Xiaoguang

doi:10.3892/mmr.2011.494

Cited by 15 publications

(17 citation statements)

References 22 publications

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“…6A) [27]. However, NPB304 had no significant effect on P-gp expression in either MX-1/paclitaxel or MCF-7/paclitaxel cells.…”

Section: Resultsmentioning

confidence: 87%

“…Co-administration of NPB304 with paclitaxel increased paclitaxel accumulation in tumor tissue [27] and Caco-2 cells, both of which overexpress P-gp. Overexpression of P-gp was identified as the main factor mediating MDR in various types of resistant cancer [54], [55]; thus, we examined the effect of NPB304 on the transport function and expression of P-gp.…”

Section: Discussionmentioning

confidence: 96%

“…The human breast cancer cell line MX-1 and its resistant derivative MX-1/paclitaxel [25] were generously provided by Professor Yongkui Jing (Mount Sinai School of Medicine, New York, USA) [26], [27]. The human breast cancer cell line MCF-7 was purchased from ATCC.…”

Section: Methodsmentioning

confidence: 99%

“…The human breast cancer cell line MCF-7 was purchased from ATCC. MCF-7/paclitaxel was established by continuous stepwise exposure to paclitaxel [27]. The cells were cultured in DMEM (Gibco BRL) supplemented with 10% FBS at 37°C in a humidified atmosphere with 5% CO 2 .…”

Section: Methodsmentioning

confidence: 99%

“…A paclitaxel-resistant MX-1 xenograft model [27] was employed. Tumor resistance was achieved in the flank of female nude mice after eight passages (30 mg/kg paclitaxel per passage).…”

Section: Methodsmentioning

confidence: 99%

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A New 2α,5α,10β,14β-tetraacetoxy-4(20),11-taxadiene (SIA) Derivative Overcomes Paclitaxel Resistance by Inhibiting MAPK Signaling and Increasing Paclitaxel Accumulation in Breast Cancer Cells

et al. 2014

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Tumor resistance due to multiple mechanisms seriously hinders the efficacy of chemotherapy drugs such as paclitaxel. The most widely studied P-glycoprotein inhibitors still have limited ability to reverse resistance in the clinic. In this study, NPB304, a novel Sinenxan A (SIA) derivative, was found to significantly sensitize resistant breast cancer cells to paclitaxel in vitro and in vivo. Treatment with NPB304 increased paclitaxel-induced apoptosis in a p53-dependent manner through PARP cleavage. Importantly, NPB304 enhanced the antitumor effect of paclitaxel in resistant breast tumor xenografts in nude mice without significantly affecting weight loss. NPB304 regulated cell resistance through inhibition of MAPK pathway components, including p-ERK and p-p38. Moreover, NPB304 increased paclitaxel accumulation by affecting P-gp function. In addition to increasing Rhodamine 123 accumulation, NPB304 promoted bidirectional permeability but decreased the efflux ratio of paclitaxel in a Caco-2 monolayer model, thereby increasing the intracellular concentration of paclitaxel. Similarly, NPB304 increased the concentration of paclitaxel in the resistant tumor tissue. Hence, NPB304 is a novel compound that promotes the sensitization of resistant cells to paclitaxel through multiple mechanisms and has the potential for use in combination therapies to treat resistant breast cancer.

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“…6A) [27]. However, NPB304 had no significant effect on P-gp expression in either MX-1/paclitaxel or MCF-7/paclitaxel cells.…”

Section: Resultsmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 96%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…A paclitaxel-resistant MX-1 xenograft model [27] was employed. Tumor resistance was achieved in the flank of female nude mice after eight passages (30 mg/kg paclitaxel per passage).…”

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

A New 2α,5α,10β,14β-tetraacetoxy-4(20),11-taxadiene (SIA) Derivative Overcomes Paclitaxel Resistance by Inhibiting MAPK Signaling and Increasing Paclitaxel Accumulation in Breast Cancer Cells

et al. 2014

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Identification and characterization of deschloro-chlorothricin obtained from a large natural product library targeting aurora A kinase in multiple myeloma

Özenver

Abdelfatah

Klinger³

et al. 2020

Invest New Drugs

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SummaryMultiple myeloma (MM) is a devastating disease with low survival rates worldwide. The mean lifetime of patients may be extendable with new drug alternatives. Aurora A kinase (AURKA) is crucial in oncogenesis, because its overexpression or amplification may incline the development of various types of cancer, including MM. Therefore, inhibitors of AURKA are innovative and promising targets. Natural compounds always represented a valuable resource for anticancer drug development. In the present study, based on virtual drug screening of more than 48,000 natural compounds, the antibiotic deschloro-chlorotricin (DCCT) has been identified to bind to AURKA with even higher binding affinity (free bindung energy: −12.25 kcal/mol) than the known AURKA inhibitor, alisertib (free binding energy: −11.25 kcal/mol). The in silico studies have been verified in vitro by using microscale thermophoresis. DCCT inhibited MM cell lines (KMS-11, L-363, RPMI-8226, MOLP-8, OPM-2, NCI-H929) with IC50 values in a range from 0.01 to 0.12 μM. Furthermore, DCCT downregulated AURKA protein expression, induced G2/M cell cycle arrest and disturbed the cellular microtubule network as determined by Western blotting, flow cytometry, and fluorescence microscopy. Thus, DCCT may be a promising lead structure for further derivatization and the development of specific AURKA inhibitors in MM therapy.

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Combination of AURKA inhibitor and HSP90 inhibitor to treat breast cancer with AURKA overexpression and TP53 mutations

Wang

Zhang²,

Wang³

et al. 2022

Med Oncol

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Function of Aurora kinase A in Taxol-resistant breast cancer and its correlation with P-gp

Abstract: Abstract. Breast cancer is one of the most common malignant diseases among women. In early and metastatic breast cancer,

Cited by 15 publications

References 22 publications

A New 2α,5α,10β,14β-tetraacetoxy-4(20),11-taxadiene (SIA) Derivative Overcomes Paclitaxel Resistance by Inhibiting MAPK Signaling and Increasing Paclitaxel Accumulation in Breast Cancer Cells

A New 2α,5α,10β,14β-tetraacetoxy-4(20),11-taxadiene (SIA) Derivative Overcomes Paclitaxel Resistance by Inhibiting MAPK Signaling and Increasing Paclitaxel Accumulation in Breast Cancer Cells

Identification and characterization of deschloro-chlorothricin obtained from a large natural product library targeting aurora A kinase in multiple myeloma

Combination of AURKA inhibitor and HSP90 inhibitor to treat breast cancer with AURKA overexpression and TP53 mutations

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