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.

对现有抗癌药物的多药耐药性的发展是癌症治疗中的主要挑战之一。据报道，细胞色素P450 1B1酶的过表达引起对顺铂的耐药。以客观发现顺铂耐药性逆转剂，在此，我们报道的评价光果甘草（甘草）提取物和其12种化学成分在Sacchrosomes CYP1B1（和CYP1A1）酶的抑制和活的人类细胞。该水醇提取物在酵母菌体和活细胞中均显示出对CYP1B1的有效抑制作用，IC ₅₀值分别为21和16 µg / mL。在总共测试的12种成分中，槲皮素和glabrol在使用IC _50的活细胞测定中显示出对CYP1B1的抑制作用值分别为2.2和15 µM。发现这两种天然产物都是CYP1B1的选择性抑制剂，并且不抑制CYP2和CYP3酶家族（IC ₅₀  > 20 µM）。G. glabra和槲皮素的水醇提取物（4）在过量表达CYP1B1的三阴性MDA-MB-468乳腺癌细胞中显示出对顺铂耐药性的完全逆转。通过分子模型研究了槲皮素和萘丙酚对CYP2和CYP3酶家族的选择性抑制作用。