Review
Biochemistry & Molecular Biology
Peter Szatmari, Eszter Ducza
Summary: ABC transporters are essential for drug efflux in the human body, with significant impact on pharmacokinetics and pharmacologic properties of drugs. P-gp and BCRP transporters, in particular, play a crucial role in barrier tissues. During pregnancy, placental and intestinal ABC transporters are of great importance for drug absorption and distribution. Their expression changes with gestational age and can affect the efficacy of various therapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Chao-Yun Cai, Qiu-Xu Teng, Megumi Murakami, Suresh V. Ambudkar, Zhe-Sheng Chen, Vijaya L. Korlipara
Summary: A series of 22 quinazolinamine derivatives with potent inhibitory activities on BCRP and P-gp were synthesized. Compound 22 was identified as a dual BCRP and P-gp inhibitor, while compound 33 showed BCRP inhibitory activity. These compounds changed the localization of BCRP and P-gp, inhibiting the efflux of anticancer drugs by the two ABC transporters. Compounds 22 and 33 also stimulated ATP hydrolysis, increasing the accumulation of mitoxantrone in BCRP-overexpressing cells.
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
Kamila Siedlecka-Kroplewska, Agata Wronska, Zbigniew Kmiec
Summary: Acute myeloid leukemia is characterized by uncontrolled proliferation of abnormal myeloid progenitor cells. Despite recent advances in treatment, prognosis remains poor, driving the search for new chemotherapeutics. Piceatannol shows promise as a chemotherapeutic agent for leukemia, but its use may be associated with the risk of multidrug resistance, suggesting the need for combination therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
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)
Review
Obstetrics & Gynecology
Elizabeth Asztalos, Kellie E. Murphy, Stephen G. Matthews
Summary: Synthetic antenatal corticosteroids are commonly used in women at risk for preterm birth before 34 weeks of gestation, but there are concerns about their potential long-term effects on the fetal brain. Further research is needed to gather sufficient safety data, both short term and long term. Caution should be exercised in the use of antenatal corticosteroids until dosing strategies can be optimized and better identification of women at risk of preterm birth is achieved.
AMERICAN JOURNAL OF PERINATOLOGY
(2022)
Article
Endocrinology & Metabolism
Hailey Scott, Lilian M. Martinelli, David Grynspan, Enrrico Bloise, Kristin L. Connor
Summary: Preterm birth and infection can alter placental expression of multidrug resistance transporters and IL-6, while maternal prepregnancy BMI does not influence placental outcomes.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Review
Obstetrics & Gynecology
Lilian M. Martinelli, Antonio Carucci, Victor J. H. Payano, Kristin L. Connor, Enrrico Bloise
Summary: The yolk sac (YS) is an important extraembryonic membrane in vertebrates. This review compares the developmental aspects and functions of the YS in humans and mice, and highlights the similarities and differences between the two species. Despite some dissimilarities, the mouse can potentially serve as a translational model for studying the human YS.
REPRODUCTIVE SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Margaret Elizabeth Eng, Enrrico Bloise, Stephen G. Matthews
Summary: Maternal antenatal use of synthetic glucocorticoids (sGCs) can affect blood-brain barrier (BBB) function in juvenile offspring, with potential sex differences.
Review
Biochemistry & Molecular Biology
Margaret E. Eng, Guinever E. Imperio, Enrrico Bloise, Stephen G. Matthews
Summary: The blood-brain barrier plays an important role in protecting the developing brain from environmental toxins and xenobiotics. Drug transporters, such as P-gp and BCRP, are crucial for developmental homeostasis and fetal brain protection. Various factors can modulate the expression and function of these drug transporters, either increasing or inhibiting brain protection.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Pediatrics
Jennifer M. Lye, Julia A. Knight, Jasleen Arneja, Ryan A. Seeto, Jody Wong, Nadya Adel Khani, Jennifer D. Brooks, Robert D. Levitan, Stephen G. Matthews, Stephen J. Lye, Rayjean J. Hung
Summary: This study aimed to investigate the relationship between maternal acetaminophen use during pregnancy and cognitive development at 4 years old. Through data analysis and regression models, the study found no association between acetaminophen use and cognitive development in offspring.
PEDIATRIC RESEARCH
(2023)
Article
Multidisciplinary Sciences
V. R. S. Monteiro, C. B. V. Andrade, H. R. Gomes, M. W. Reginatto, G. E. Imperio, K. N. Fontes, D. A. Spiess, W. S. Rangel-Junior, V. M. O. Nascimento, C. O. S. Lima, R. P. C. Sousa, F. F. Bloise, S. G. Matthews, E. Bloise, P. M. Pimentel-Coelho, T. M. Ortiga-Carvalho
Summary: Limited information is available about the effect of mid-pregnancy viral infections on placental expression and offspring behavior. This study found that maternal exposure to a synthetic double-stranded RNA viral mimic disrupted placental cell turnover and impaired offspring behavior in adult life.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Kristin L. Connor, Enrrico Bloise, Todd Z. DeSantis, Stephen J. Lye
Summary: This study explores the effects of malnutrition on gut structure and function in pregnant women and highlights the adaptive changes in the gut holobiont in response to suboptimal maternal diets. Specifically, a high-fat diet increases maternal small intestinal architecture and proinflammatory load while decreasing the expression of P-glycoprotein. On the other hand, undernutrition increases small intestinal villi proliferation and the expression of certain MDR transporters, but decreases the expression of Abcg2. Furthermore, specific microbial taxa are significantly associated with the levels of MDR transporter expression.
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
C. B. V. Andrade, L. V. A. Lopes, T. M. Ortiga-Carvalho, S. G. Matthews, E. Bloise
Summary: This review comprehensively examines the effect of infection on the placental multidrug resistance (MDR) transporters P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), finding that infection can regulate the expression of P-gp and BCRP in the placenta by altering their mRNA, protein, and function levels. The modulation effect varies according to different infection factors, gestational age, trophoblast type, and species. The expression and localization of Toll-like receptor (TLR) proteins at the maternal-fetal interface are also discussed, aiming to understand how infective agents modulate placental MDR. The alterations in placental MDR induced by infection may impact the distribution of important MDR substrates and adversely affect pregnancy outcome and maternal/neonatal health.
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2023)
Article
Neurosciences
Phetcharawan Lye, Enrrico Bloise, Stephen G. G. Matthews
Summary: Infectious pathogen-associated molecular patterns (PAMPs) significantly modify the expression and function of multidrug resistance (MDR) transporters in human fetal brain endothelial cells (hfBECs), potentially leading to altered trajectories of fetal brain development.
FLUIDS AND BARRIERS OF THE CNS
(2023)
Review
Microbiology
Thaina Ferraz, Samantha J. Benton, Israa Zareef, Oluwatomike Aribaloye, Enrrico Bloise, Kristin L. Connor
Summary: Obesity is a risk factor for severe COVID-19 disease during pregnancy. The co-occurrence of high maternal BMI and gestational SARS-CoV-2 infection are detrimental to fetoplacental development. In pregnancies with high maternal BMI and SARS-CoV-2 infection, chronic inflammation, fetal vascular malperfusion, maternal vascular malperfusion, and fibrinoids were commonly observed placental lesions.
Article
Obstetrics & Gynecology
Hafsah Mughis, Phetcharawan Lye, Stephen G. Matthews, Enrrico Bloise
Summary: This study found that human fetal brain endothelial cells express SARS-CoV-2-associated cell entry proteins during early and mid-pregnancy. Hypoxia can modify the expression levels of these proteins in a gestational age and time-of-exposure-dependent manner.
AMERICAN JOURNAL OF OBSTETRICS & GYNECOLOGY MFM
(2023)
Article
Biology
F. Aguiar, P. Rhana, E. Bloise, C. B. Nunes, A. L. Rodrigues, E. Ferreira
Summary: The protein expression and subcellular localization of T-type voltage-dependent Ca2+ channels (Cav3) were evaluated in human breast tissue samples. It was found that the nuclear expressions of CaV3.1, CaV3.2, and CaV3.3 decreased in advanced stages of neoplastic transformation, while the cytoplasmic expression of CaV3.1 and CaV3.2 increased. The change in protein expression and subcellular localization of CaV3 corresponded with the neoplastic transformation stages, suggesting a possible involvement of CaV3 in the carcinogenic processes and its potential as a pharmacological target in breast cancer treatment.
BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH
(2023)
Article
Neurosciences
Thiago A. Andrade, Julia S. Fahel, Jessica M. De Souza, Ana C. Terra, Danielle G. Souza, Vivian V. Costa, Mauro M. Teixeira, Enrrico Bloise, Fabiola M. Ribeiro
Summary: In utero exposure to Zika virus (ZIKV) during early pregnancy may lead to neurological alterations in adulthood, with female mice being more susceptible than males. The exposure to ZIKV resulted in significant neuronal cell loss and decreased expression of important genes and synaptic markers related to neuronal function and synaptic plasticity. Female mice exposed to ZIKV also exhibited risk-taking behavior and deficits in spatial memory.
Meeting Abstract
Obstetrics & Gynecology
Hafsah Mughis, Phetcharawan Lye, Guinever Imperio, Enrrico Bloise, Stephen Matthews
REPRODUCTIVE SCIENCES
(2022)
