ABC-transporter blockage mediated by xanthotoxin and bergapten is the major pathway for chemosensitization of multidrug-resistant cancer cells

Toxicology and Applied Pharmacology
Seyed Abbas MirzaeiFatemeh Elahian

Abstract

Furanocoumarins derived from herbal and citrus extracts can act as antibacterial, antioxidant, immunomodulator, apoptotic, and selective anticancer agents, prompting a biological investigation to determine and predict their clinical therapeutic significance. Here, the cell cytotoxic effects of bergapten and xanthotoxin were analyzed alone and in combination with standard chemotherapeutics on three multidrug resistant cells and their nonresistant parental counterparts. The furanocoumarins modulatory effects on MDR1, BCRP, and MRP pump expression and function were investigated. Although quantitative real time PCR demonstrated that the MDR transcript level changes in a time dependent manner, flow cytometric analyses using fluorescent-labeled antibodies have indicated that bergapten and xanthotoxin had no significant effect on the protein levels. FACS analyses indicated that these prominent anticancer agents significantly blocked MDR1, BCRP, and MRP transporter function. Maximum furanocoumarin-mediated pump activity blockage in the MDR-resistant cells was quantified as 87% of normal and consequently, chemotherapeutic accumulation increased up to 2.7-fold and cytotoxicity tension increased 104-fold. MDR1 efflux kinetics also reveale...Continue Reading

Citations

May 10, 2019·Pharmaceutical Biology·Javad MottaghipishehDezső Csupor
Mar 17, 2020·Frontiers in Oncology·Jingqiu WangZhe-Sheng Chen
Aug 13, 2020·International Journal of Molecular Sciences·Salman AhmedRaffaele Capasso
Sep 9, 2019·Life Sciences·Seyed Abbas MirzaeiFatemeh Elahian
Jan 13, 2021·International Journal of Molecular Sciences·Paula Wróblewska-ŁuczkaJarogniew J Łuszczki
Feb 18, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Imran Shair MohammadLifang Yin
Aug 5, 2021·Phytotherapy Research : PTR·Youdan LiangXiaofang Li
Oct 22, 2021·Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP·Kan FuYanping Luo

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