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Glycyrrhiza glabra extract and quercetin reverses cisplatin resistance in triple-negative MDA-MB-468 breast cancer cells via inhibition of cytochrome P450 1B1 enzyme

Jain, Shreyans K.; Vishwakarma, Ram A.; Chaudhuri, Bhabatosh; Bharate, Sandip B.; Williams, Ibidapo S; Sharma, Rajni; Gatchie, Linda

Authors

Shreyans K. Jain

Ram A. Vishwakarma

Bhabatosh Chaudhuri

Sandip B. Bharate

Ibidapo Williams Ibidapo.Williams@uwe.ac.uk
Research Fellow- Cell Cultural Monitoring Technology

Rajni Sharma

Linda Gatchie



Abstract

© 2017 Elsevier Ltd The development of multi-drug resistance to existing anticancer drugs is one of the major challenges in cancer treatment. The over-expression of cytochrome P450 1B1 enzyme has been reported to cause resistance to cisplatin. With an objective to discover cisplatin-resistance reversal agents, herein, we report the evaluation of Glycyrrhiza glabra (licorice) extracts and its twelve chemical constituents for inhibition of CYP1B1 (and CYP1A1) enzyme in Sacchrosomes and live human cells. The hydroalcoholic extract showed potent inhibition of CYP1B1 in both Sacchrosomes as well as in live cells with IC50 values of 21 and 16 µg/mL, respectively. Amongst the total of 12 constituents tested, quercetin and glabrol showed inhibition of CYP1B1 in live cell assay with IC50 values of 2.2 and 15 µM, respectively. Both these natural products were found to be selective inhibitors of CYP1B1, and does not inhibit CYP2 and CYP3 family of enzymes (IC50 > 20 µM). The hydroalcoholic extract of G. glabra and quercetin (4) showed complete reversal of cisplatin resistance in CYP1B1 overexpressing triple negative MDA-MB-468 breast cancer cells. The selective inhibition of CYP1B1 by quercetin and glabrol over CYP2 and CYP3 family of enzymes was studied by molecular modeling studies.

Citation

Bharate, S. B., Chaudhuri, B., Vishwakarma, R. A., Jain, S. K., Sharma, R., Gatchie, L., & Williams, I. S. (2017). Glycyrrhiza glabra extract and quercetin reverses cisplatin resistance in triple-negative MDA-MB-468 breast cancer cells via inhibition of cytochrome P450 1B1 enzyme. Bioorganic and Medicinal Chemistry Letters, 27(24), 5400-5403. https://doi.org/10.1016/j.bmcl.2017.11.013

Journal Article Type Article
Acceptance Date Nov 6, 2017
Online Publication Date Nov 7, 2017
Publication Date Dec 15, 2017
Deposit Date May 9, 2018
Journal Bioorganic and Medicinal Chemistry Letters
Print ISSN 0960-894X
Electronic ISSN 1464-3405
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 27
Issue 24
Pages 5400-5403
DOI https://doi.org/10.1016/j.bmcl.2017.11.013
Keywords cisplatin-resistance, CYP1B1, glycyrrhiza glabra, quercetin, glabrol, MDA-MB-468 cells
Public URL https://uwe-repository.worktribe.com/output/878825
Publisher URL https://doi.org/10.1016/j.bmcl.2017.11.013