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Cited by 282

The DOI matches its Crossref record; 77 of the 77 references it cites were found in a registry or an index.

Targeted inhibitors of P-glycoprotein increase chemotherapeutic-induced mortality of multidrug resistant tumor cells

Open access
Nanayakkara, Amila K., Follit, Courtney A., Chen, Gang, Williams, Noelle S., Vogel, Pia D., Wise, John G.·2018·Scientific Reports
DOI 10.1038/s41598-018-19325-x
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Abstract

Overexpression of ATP-binding cassette (ABC) transporters is often linked to multidrug resistance (MDR) in cancer chemotherapies. P-glycoprotein (P-gp) is one of the best studied drug transporters associated with MDR. There are currently no approved drugs available for clinical use in cancer chemotherapies to reverse MDR by inhibiting P-glycoprotein. Using computational studies, we previously identified several compounds that inhibit P-gp by targeting its nucleotide binding domain and avoiding its drug binding domains. Several of these compounds showed successful MDR reversal when tested on a drug resistant prostate cancer cell line. Using conventional two-dimensional cell culture of MDR ovarian and prostate cancer cells and three dimensional prostate cancer microtumor spheroids, we demonstrated here that co-administration with chemotherapeutics significantly decreased cell viability and survival as well as cell motility. The P-gp inhibitors were not observed to be toxic on their own. The inhibitors increased cellular retention of chemotherapeutics and reporter compounds known to be transport substrates of P-gp. We also showed that these compounds are not transport substrates of P-gp and that two of the three inhibit P-gp, but not the closely related ABC transporter, ABCG2/BCRP. The results presented suggest that these P-gp inhibitors may be promising leads for future drug development.

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Metadata

Authors
Nanayakkara, A. K., Follit, C. A., Chen, G., Williams, N. S., Vogel, P. D., & Wise, J. G.
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2018-01-17
Volume
8
Issue
1
Pages
967-967
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-018-19325-x
OpenAlex
W2783056471
Cited by
282
References
77
FWCI
11.96
Type
journal article
Language
en
Open access
gold

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CoChat. (2026). Citation check: Targeted inhibitors of P-glycoprotein increase chemotherapeutic-induced mortality of multidrug resistant tumor cells. https://app.cochat.ai/papers/10.1038/s41598-018-19325-x
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Nanayakkara, A. K., Follit, C. A., Chen, G., Williams, N. S., Vogel, P. D., & Wise, J. G. (2018). Targeted inhibitors of P-glycoprotein increase chemotherapeutic-induced mortality of multidrug resistant tumor cells. Scientific Reports. https://doi.org/10.1038/s41598-018-19325-x

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Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.