Neomangiferin Overcomes ABCB1-Mediated Multidrug Resistance in Cancer and Its Mechanisms

LIN Ruihui^1#, SHAO Xulong^1#, YU Tao^1#, HOU Xinyu¹, SHANG Zilin¹, DONG Xinduo², PAN Zhifang1*, FENG Weiguo¹*

(¹School of Life Science and Technology, Shandong Second Medical University, Weifang 261053, China;²College of Pharmacy and Health Sciences, St. John’s University, New York 11439, USA)

Abstract:

The overexpression of P-glycoprotein (ABCB1/P-gp) is a key factor in causing MDR (multi drug resistance) in cancers. Therefore, it is crucial to discover effective drugs against ABCB1 to overcome MDR. Neomangiferin, a polyphenolic carbonyl glycoside compound derived from Anemarrhenae Rhizoma, has anti inflammatory, antioxidant and anti-tumor properties. This study investigated whether Neomangiferin could effec tively overcome ABCB1-mediated MDR and its mechanism. The result of network pharmacology assay showed that Neomangiferin, the active ingredient of Anemarrhenae Rhizoma, was closely related to ABCB1. The results of MTT and colony formation assays indicated that Neomangiferin could effectively overcome ABCB1-mediated MDR (P<0.05). The results of Western blot and immunofluorescence revealed that Neomangiferin had no effect on the expression and localization of ABCB1 protein in cells. The results of drug accumulation and efflux experiments showed that Neomangiferin increased the intracellular accumulation of chemotherapeutic drugs by inhibiting the efflux of ABCB1 protein, thus overcoming MDR. In addition, molecular docking and thermal stability experiments showed that Neomangiferin could stably bind to ABCB1 protein. In conclusion, this study found that Neomangif erin could effectively overcome ABCB1-mediated MDR, providing a novel therapeutic strategy for chemotherapy resistant tumor patients.

CSTR: 32200.14.cjcb.2024.09.0003