Article
Chemistry, Multidisciplinary
Qiwen Guan, Xuan Wang, Danfeng Cao, Menghuan Li, Zhong Luo, Xiaoyuan Mao
Summary: This study reports a nanointegrated strategy to enhance the antiepileptic efficacy of phenytoin (PHT) by overcoming drug resistance mechanisms. PHT is incorporated into calcium phosphate nanoparticles and surface modified with a PEGylated BBB-penetrating TAT peptide. The resulting CaP@PHT-PEG-TAT nanoformulation effectively crosses the blood-brain barrier, taken up by epileptic neurons and subsequently degrades to release Ca2+ and PHT. The released Ca2+ inhibits cellular hypoxia and disrupts adenosine triphosphate generation, leading to the suppression of P-glycoprotein expression and drug efflux capacity to enhance PHT retention.
Article
Chemistry, Physical
Linna Liang, Wendi Huo, Bei Wang, Lingzhi Cao, Haoran Huo, Yixin Liu, Yi Jin, Xinjian Yang
Summary: Tumor multidrug resistance is a major cause of chemotherapy failure, and reversing tumor multidrug resistance is crucial for increasing the sensitivity of tumor cells to chemodrugs. The self-assembled DNAzyme nanoflowers can efficiently reverse multidrug resistance, enhance drug loading capacity, and suppress P-glycoprotein expression.
JOURNAL OF COLLOID AND INTERFACE SCIENCE
(2022)
Article
Pharmacology & Pharmacy
Sofija Jovanovic Stojanov, Epole N. Ntungwe, Jelena Dinic, Ana Podolski-Renic, Milica Pajovic, Patricia Rijo, Milica Pesic
Summary: Coleon U, a natural compound not recognized as a substrate of P-glycoprotein, has equal efficacy against sensitive and multidrug-resistant cancer cells. It delays the decrease in P-glycoprotein activity by decreasing mitochondrial membrane potential and inhibiting P-glycoprotein expression.
Retraction
Oncology
S. Mohana, M. Ganesan, N. Rajendra Prasad, D. Ananthakrishnan, D. Velmurugan
Summary: A correction to this paper has been published and is accessible through the original article.
Review
Biochemistry & Molecular Biology
Manuela Labbozzetta, Paola Poma, Monica Notarbartolo
Summary: Acute myeloid leukemia (AML) is difficult to treat due to the development of resistance to both traditional chemotherapy and new drugs in some patients. Multidrug resistance (MDR) in AML is often caused by the overexpression of P-glycoprotein (P-gp), which is an efflux pump. This mini-review focuses on the advantages of using natural substances as inhibitors of P-gp, including phytol, curcumin, lupeol, and heptacosane, and their mechanisms of action in AML.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Oncology
Yichen Tian, Yongrong Lei, Yani Wang, Jiejuan Lai, Jianhua Wang, Feng Xia
Summary: This review summarizes the mechanisms of multidrug resistance (MDR) mediated by P-glycoprotein (P-gp), including the regulation of efflux activity, the inhibition of P-gp expression, and the knockout of the ABCB1 gene. Inhibiting P-gp through screening and designing suitable compounds and techniques can overcome P-gp-mediated MDR, providing a reference for studying the reversal of P-gp-mediated MDR.
INTERNATIONAL JOURNAL OF ONCOLOGY
(2023)
Review
Medicine, Research & Experimental
M. Ganesan, G. Kanimozhi, B. Pradhapsingh, Haseeb A. Khan, Abdullah S. Alhomida, Aishah Ekhzaimy, G. R. Brindha, N. Rajendra Prasad
Summary: The review discusses the role of natural phytochemicals in modulating ABCB1 gene expression through various signal transduction pathways in MDR cancer cells, suggesting an alternative approach to reversing MDR by downregulating P-glycoprotein expression in tumor tissues.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Agronomy
Tan Dai, Zhiwen Wang, Xingkai Cheng, Huige Gao, Li Liang, Pengfei Liu, Xili Liu
Summary: Both fungicide efflux and detoxification metabolism are involved in the resistance mechanisms of Phytophthora capsici to SYP-14288.
PEST MANAGEMENT SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Eric Chekwube Aniogo, Blassan P. George, Heidi Abrahamse
Summary: The study utilized photodynamic therapy to treat MCF-7 cells overexpressed with P-glycoprotein, resulting in cell apoptosis with increased externalisation of phosphatidylserine protein and changes in apoptotic protein expression.
Article
Oncology
Chung-Pu Wu, Cheng-Yu Hung, Megumi Murakami, Yu-Shan Wu, Chun-Ling Lin, Yang-Hui Huang, Tai-Ho Hung, Jau-Song Yu, Suresh Ambudkar
Summary: In this study, we investigate the role of P-glycoprotein (P-gp) in the reduced sensitivity of cancer cells to the anaplastic lymphoma kinase (ALK) inhibitor ensartinib. Our results demonstrate that P-gp overexpression decreases the intracellular accumulation and cytotoxic activity of ensartinib in cancer cells. These findings highlight the importance of understanding the mechanisms of ensartinib resistance mediated by P-gp.
Article
Biochemistry & Molecular Biology
Yasmeen Cheema, Yusra Sajid Kiani, Kenneth J. J. Linton, Ishrat Jabeen
Summary: Researchers developed a pharmacophore model based on the cryo-EM structure of ABCB1 to screen for new inhibitors, resulting in the identification of six potential inhibitors with distinct chemistries and favorable properties. The compounds exhibited low nanomolar range inhibitory concentrations and two of them were able to resensitize ABCB1-expressing cells to taxol. This study demonstrates the utility of cryo-electron microscopy in drug identification and design.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Ashutosh Singh, Sandesh Kumar Patel, Prateek Kumar, Kanhu Charan Das, Deepanshu Verma, Rohit Sharma, Timir Tripathi, Rajanish Giri, Natalia Martins, Neha Garg
Summary: The resistance of cancer cells to chemotherapy is a major challenge in drug discovery. P-glycoprotein (P-gp) overexpression is directly linked to multidrug resistance (MDR) in cancer cells. Quercetin has been reported to inhibit the activity of P-gp, but the underlying mechanism is not fully understood. This study reveals the mechanistic understanding of quercetin-induced modulation of P-gp using molecular docking and molecular dynamics simulation.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Biochemistry & Molecular Biology
Jason W. Y. Kan, Clare S. W. Yan, Iris L. K. Wong, Xiaochun Su, Zhen Liu, Tak Hang Chan, Larry M. C. Chow
Summary: Biotransformation of flavonoid dimer FD18 resulted in an active metabolite FM04, which exhibited improved druggability and was more potent in reversing P-gp-mediated PTX resistance. FM04 sensitized cancer cells to multiple anticancer drugs by inhibiting P-gp transport activity and stimulating P-gp ATPase. In addition, FM04 enhanced the intestinal absorption of PTX and showed significant antitumor activity in mouse models.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Shafi Mahmud, Md. Jahirul Islam, Md. Rimon Parves, Md. Arif Khan, Lamiya Tabussum, Sinthyia Ahmed, Md. Ackas Ali, Sayo O. Fakayode, Mohammad A. Halim
Summary: This study aimed to identify potent inhibitors of P-glycoprotein using computational approaches. Two compounds showed promising anti-tumor activity with acceptable pharmacokinetic properties, and molecular docking and dynamics simulations verified their stable binding with P-glycoprotein. Principal component analysis and QSAR modeling provided insights into the interactions and predictive capabilities of the drug candidates.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Cell Biology
Chung-Pu Wu, Megumi Murakami, Yu-Shan Wu, Ya-Chen Chi, Sung-Han Hsiao, Yang-Hui Huang, Tai-Ho Hung, Suresh Ambudkar
Summary: The study explored the potential of using branebrutinib to resensitize P-gp-overexpressing multidrug-resistant cancer cells to chemotherapy by inhibiting the drug transport function of P-gp. Results showed that branebrutinib could reverse P-gp-mediated MDR at sub-toxic concentrations while maintaining cytotoxicity against drug-sensitive parental cell lines and P-gp-overexpressing multidrug-resistant variants. This new pharmacological action of branebrutinib against P-gp activity warrants further investigation in future drug combination studies.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
