The study of drug resistance properties of ABCG2 (ATP-binding cassette G2) in contact with thymoquinone, gallic acid, and hesperetin antioxidants

Introduction: ATP-binding cassette (ABC) transporters are a group of intra membrane proteins that play key roles in the transmission and exchange of vital compounds on both sides of the membrane. These proteins can specially transport anti-cancer drugs out of cancer cells. ABCG2 is a member of this family that is extremely expressed in many cancers. This study, aims to evaluate the binding affinity of three antioxidants thymoquinone (TQ), gallic acid (GA), and hesperetin (HP) to ABCG2 compared with an anti-cancer drug, mitoxantrone (Mit), to export cells. Methods: The PDB file of ABCG2 was obtained from the protein data bank server (http://www.rcsb.org) with ID: 5NJ3. After 200 stages of molecular docking running on ABCG2 protein in AutoDock v.4.2 software, the amino acids involved in the binding site of each compound were identified using the LigPlot+ software. Results: HP had the lowest (-6.36 kcal/mol) and GA had the highest (-3.93 kcal/mol) binding energy in comparison with Mit (-0.06 kcal/mol) for binding to ABCG2. Effective concentration required to perform the reaction between ABCG2 was higher in GA (1.31 mM) than TQ (42.69 μM) and HP (21.74 μM). GA, HP, and TQ formed 17, 18, and 22 hydrogen and hydrophobic bonds at the binding site of ABCG2. Conclusion: It seems that GA has the lowest affinity to make contact with ABCG2 binding site. So, GA tends to remain in the cell but TQ and HP tend to leave the cell easily via ABCG2 transporter.

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Stemness and anti‐cancer drug resistance in ATP ‐binding cassette subfamily G member 2 highly expressed pancreatic cancer is induced in 3D culture conditions

Cancer Science ◽

10.1111/cas.13533 ◽

2018 ◽

Vol 109 (4) ◽

pp. 1135-1146 ◽

Cited By ~ 10

Author(s):

Norihiko Sasaki ◽

Toshiyuki Ishiwata ◽

Fumio Hasegawa ◽

Masaki Michishita ◽

Hiroki Kawai ◽

...

Keyword(s):

Pancreatic Cancer ◽

Drug Resistance ◽

3D Culture ◽

Culture Conditions ◽

Cancer Drug ◽

Atp Binding ◽

Cancer Drug Resistance ◽

Anti Cancer ◽

Atp Binding Cassette

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Growth Promotion and Increased ATP-Binding Cassette Transporters Expression by Liraglutide in Triple Negative Breast Cancer Cell Line MDA-MB-231

Drug Research ◽

10.1055/a-1345-7890 ◽

2021 ◽

Author(s):

Amir Shadboorestan ◽

Parastoo Tarighi ◽

Mahsa Koosha ◽

Homa Faghihi ◽

Mohammad Hossein Ghahremani ◽

...

Keyword(s):

Breast Cancer ◽

Cell Line ◽

Triple Negative Breast Cancer ◽

Abc Transporters ◽

Triple Negative ◽

Epithelial Mesenchymal Transition ◽

Growth Promotion ◽

Atp Binding ◽

Mesenchymal Transition ◽

Atp Binding Cassette

Background Glucagon-like petide-1 (GLP-1) agonists such as liraglutide are widely employed in type 2 diabetes due to their glucose reducing properties and small risk of hypoglycemia. Recently, it has been shown that GLP-1agonists can inhibit breast cancer cells growth. Nonetheless, concerns are remained about liraglutide tumor promoting effects as stated by population studies. Material and Methods We evaluated the effects liraglutide on proliferation of MDA-MB-231 cells by MTT assay and then ATP-binding cassette (ABC) transporters expressions assessed by Real time PCR. Statistical comparisons were made using one-way analysis of variance followed by a post hoc Dunnett test. Results Here, we report that liraglutide can stimulate the growth of highly invasive triple negative cell line MDA-MB-231; which can be attributed to AMPK-dependent epithelial-mesenchymal transition (EMT) happening in MDA-MB-231 context. Toxicity effects were only observed with concentrations far above the serum liraglutide concentration. ATP-binding cassette (ABC) transporters expressions were upregulated, indicating the possible drug resistance and increased EMT. Conclusion In conclusion, these results suggest that liraglutide should be used with caution in patients who are suffering or have the personal history of triple negative breast cancer. However, more detailed studies are required to deepen understanding of liraglutide consequences in triple negative breast cancer. ▶Graphical Abstract.

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Genome-wide analysis of ATP-binding cassette (ABC) transporters in the sweetpotato whitefly, Bemisia tabaci

BMC Genomics ◽

10.1186/s12864-017-3706-6 ◽

2017 ◽

Vol 18 (1) ◽

Cited By ~ 25

Author(s):

Lixia Tian ◽

Tianxue Song ◽

Rongjun He ◽

Yang Zeng ◽

Wen Xie ◽

...

Keyword(s):

Bemisia Tabaci ◽

Abc Transporters ◽

Atp Binding ◽

Sweetpotato Whitefly ◽

Genome Wide Analysis ◽

Genome Wide ◽

Atp Binding Cassette

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Correction to: ATP binding cassette (ABC) transporters: expression and clinical value in glioblastoma

Journal of Neuro-Oncology ◽

10.1007/s11060-018-2830-8 ◽

2018 ◽

Vol 138 (3) ◽

pp. 487-487

Author(s):

Antonin Dréan ◽

Shai Rosenberg ◽

François-Xavier Lejeune ◽

Larissa Goli ◽

Aravindan Arun Nadaradjane ◽

...

Keyword(s):

Abc Transporters ◽

Atp Binding ◽

Clinical Value ◽

Atp Binding Cassette

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Expression of some ATP-binding cassette transporters in acute myeloid leukemia

Hematology Reports ◽

10.4081/hr.2017.7406 ◽

2017 ◽

Vol 9 (4) ◽

Cited By ~ 5

Author(s):

Antonella Maria Salvia ◽

Flavia Cuviello ◽

Sabrina Coluzzi ◽

Roberta Nuccorini ◽

Immacolata Attolico ◽

...

Keyword(s):

Bone Marrow ◽

Acute Myeloid Leukemia ◽

Abc Transporters ◽

Healthy Subjects ◽

Myeloid Leukemia ◽

Resistance Mechanisms ◽

Atp Binding ◽

Atp Binding Cassette Transporters ◽

Acute Myeloid ◽

Atp Binding Cassette

Hematopoietic cells express ATP binding cassette (ABC) transporters in relation to different degrees of differentiation. One of the known multidrug resistance mechanisms in acute myeloid leukemia (AML) is the overexpression of efflux pumps belonging to the superfamily of ABC transporters such as ABCB1, ABCG2 and ABCC1. Although several studies were carried out to correlate ABC transporters expression with drug resistance, little is known about their role as markers of diagnosis and progression of the disease. For this purpose we investigated the expression, by real-time PCR, of some ABC genes in bone marrow samples of AML patients at diagnosis and after induction therapy. At diagnosis, ABCG2 was always down-regulated, while an up regulated trend for ABCC1 was observed. After therapy the examined genes showed a different expression trend and approached the values of healthy subjects suggesting that this event could be considered as a marker of AML regression. The expression levels of some ABC transporters such as ABCC6, seems to be related to gender, age and to the presence of FLT3/ITD gene mutation.

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Stickleback embryos use ATP-binding cassette transporters as a buffer against exposure to maternally derived cortisol

Proceedings of The Royal Society B Biological Sciences ◽

10.1098/rspb.2015.2838 ◽

2016 ◽

Vol 283 (1826) ◽

pp. 20152838 ◽

Cited By ~ 17

Author(s):

Ryan T. Paitz ◽

Syed Abbas Bukhari ◽

Alison M. Bell

Keyword(s):

Abc Transporters ◽

Gasterosteus Aculeatus ◽

Transcriptional Response ◽

Threespine Stickleback ◽

Egg Laying ◽

Atp Binding ◽

Active Efflux ◽

Atp Binding Cassette Transporters ◽

Stress Influences ◽

Atp Binding Cassette

Offspring from females that experience stressful conditions during reproduction often exhibit altered phenotypes and many of these effects are thought to arise owing to increased exposure to maternal glucocorticoids. While embryos of placental vertebrates are known to regulate exposure to maternal glucocorticoids via placental steroid metabolism, much less is known about how and whether egg-laying vertebrates can control their steroid environment during embryonic development. We tested the hypothesis that threespine stickleback ( Gasterosteus aculeatus ) embryos can regulate exposure to maternal steroids via active efflux of maternal steroids from the egg. Embryos rapidly (within 72 h) cleared intact steroids, but blocking ATP-binding cassette (ABC) transporters inhibited cortisol clearance. Remarkably, this efflux of cortisol was sufficient to prevent a transcriptional response of embryos to exogenous cortisol. Taken together, these findings suggest that, much like their placental counterparts, developing fish embryos can actively regulate their exposure to maternal cortisol. These findings highlight the fact that even in egg-laying vertebrates, the realized exposure to maternal steroids is mediated by both maternal and embryonic processes and this has important implications for understanding how maternal stress influences offspring development.

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