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Article ; Online: Metformin: A Dual-Role Player in Cancer Treatment and Prevention.

Galal, Mariam Ahmed / Al-Rimawi, Mohammed / Hajeer, Abdurrahman / Dahman, Huda / Alouch, Samhar / Aljada, Ahmad

International journal of molecular sciences

2024 Volume 25, Issue 7

Abstract: Cancer continues to pose a significant global health challenge, as evidenced by the increasing incidence rates and high mortality rates, despite the advancements made in chemotherapy. The emergence of chemoresistance further complicates the effectiveness ...

Abstract	Cancer continues to pose a significant global health challenge, as evidenced by the increasing incidence rates and high mortality rates, despite the advancements made in chemotherapy. The emergence of chemoresistance further complicates the effectiveness of treatment. However, there is growing interest in the potential of metformin, a commonly prescribed drug for type 2 diabetes mellitus (T2DM), as an adjuvant chemotherapy agent in cancer treatment. Although the precise mechanism of action of metformin in cancer therapy is not fully understood, it has been found to have pleiotropic effects, including the modulation of metabolic pathways, reduction in inflammation, and the regulation of cellular proliferation. This comprehensive review examines the anticancer properties of metformin, drawing insights from various studies conducted in vitro and in vivo, as well as from clinical trials and observational research. This review discusses the mechanisms of action involving both insulin-dependent and independent pathways, shedding light on the potential of metformin as a therapeutic agent for different types of cancer. Despite promising findings, there are challenges that need to be addressed, such as conflicting outcomes in clinical trials, considerations regarding dosing, and the development of resistance. These challenges highlight the importance of further research to fully harness the therapeutic potential of metformin in cancer treatment. The aims of this review are to provide a contemporary understanding of the role of metformin in cancer therapy and identify areas for future exploration in the pursuit of effective anticancer strategies.
MeSH term(s)	Humans ; Metformin/pharmacology ; Metformin/therapeutic use ; Diabetes Mellitus, Type 2/drug therapy ; Cell Proliferation ; Chemotherapy, Adjuvant ; Hyperplasia ; Neoplasms/drug therapy
Chemical Substances	Metformin (9100L32L2N)
Language	English
Publishing date	2024-04-06
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms25074083
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Article ; Online: Lipopolysaccharides-Induced Inflammatory Response in White Blood Cells Is Associated with Alterations in Senescence Mediators: Modulation by Metformin.

Aljada, Ahmad

Metabolic syndrome and related disorders

2015 Volume 13, Issue 6, Page(s) 278–285

Abstract: Background: Sirtuin (SirT), a family of conserved histone deacetylases and transferases, has been proposed to function in inflammatory, cancer, and metabolic diseases. However, it is unclear how SirT modulates these processes. In this study, the effect ... ...

Abstract	Background: Sirtuin (SirT), a family of conserved histone deacetylases and transferases, has been proposed to function in inflammatory, cancer, and metabolic diseases. However, it is unclear how SirT modulates these processes. In this study, the effect of metformin on senescence and antisenescence mediators (SirT1-7, p53, and p16(INK4a)) mRNA expression in white blood cells (WBCs) following lipopolysaccharides (LPS)-induced inflammation in mice was examined. Material and methods: C57BL/6 mice were treated with metformin in their drinking water (2 mg/mL) for 1 week followed by intraperitoneal injection of LPS from Escherichia coli serotype 0111:B4 at 2 mg/kg. Blood was collected at the basal level and 1, 2, and 3 hr after LPS injection. SirT1-7, p53, and p16(INK4a) mRNA expression in WBCs was measured by real-time quantitative polymerase chain reaction (RT-qPCR). Results: SirT7 at 2 hr, SirT1 at 3 hr, and p16(INK4a) at 1 hr were inhibited significantly in WBCs following LPS injection. There were no significant changes in other SirT nor p53 mRNA expression in WBCs after LPS injection. Metformin inhibited SirT2 expression in WBCs significantly (P<0.05) and did not induce any significant changes in other SirT forms and p53, whereas it induced p16(INK4a) mRNA expression in WBCs (P<0.05) at the basal levels. Additionally, metformin treatment significantly inhibited SirT7, SirT1, and p16(INK4a) mRNA expression in WBCs at 1, 2, and 3 hr, whereas p53 was inhibited significantly at 2 hr after LPS injection. Conclusions: SirT7 and SirT1 are stress responsive proteins that may mediate inflammation. The data suggest that metformin may exert its potential antisenescence and anti-inflammatory effects by targeting SirT7 and SirT1 pathways. SirT7 inhibition may allow the healing process and prevention of tissue damage by enabling cells to survive through inhibition of cytokines and inflammatory mediators under severe stress conditions.
MeSH term(s)	Animals ; Anti-Inflammatory Agents/pharmacology ; Cellular Senescence/drug effects ; Cyclin-Dependent Kinase Inhibitor p16/blood ; Cyclin-Dependent Kinase Inhibitor p16/genetics ; Disease Models, Animal ; Gene Expression Regulation ; Inflammation/blood ; Inflammation/chemically induced ; Inflammation/drug therapy ; Inflammation/genetics ; Inflammation Mediators/blood ; Leukocytes/drug effects ; Leukocytes/metabolism ; Lipopolysaccharides ; Male ; Metformin/pharmacology ; Mice, Inbred C57BL ; RNA, Messenger/blood ; Real-Time Polymerase Chain Reaction ; Sirtuins/blood ; Sirtuins/genetics ; Time Factors ; Tumor Suppressor Protein p53/blood ; Tumor Suppressor Protein p53/genetics
Chemical Substances	Anti-Inflammatory Agents ; Cdkn2a protein, mouse ; Cyclin-Dependent Kinase Inhibitor p16 ; Inflammation Mediators ; Lipopolysaccharides ; RNA, Messenger ; Tumor Suppressor Protein p53 ; lipopolysaccharide, Escherichia coli O111 B4 ; Metformin (9100L32L2N) ; Sirtuins (EC 3.5.1.-)
Language	English
Publishing date	2015-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2151220-6
ISSN	1557-8518 ; 1540-4196
ISSN (online)	1557-8518
ISSN	1540-4196
DOI	10.1089/met.2014.0168
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Article ; Online: Bioanalysis of plasma acetate levels without derivatization by LC-MS/MS.

Qasem, Rani J / Frah, Ibrahim K / Aljada, Ahmad S / Sehli, Faisal A

Bioanalysis

2021 Volume 13, Issue 5, Page(s) 373–386

Abstract: Background: ...

Abstract	Background:
MeSH term(s)	Acetates/blood ; Biological Assay ; Chromatography, Liquid ; Humans ; Tandem Mass Spectrometry
Chemical Substances	Acetates
Language	English
Publishing date	2021-03-04
Publishing country	England
Document type	Journal Article
ISSN	1757-6199
ISSN (online)	1757-6199
DOI	10.4155/bio-2020-0294
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Article ; Online: Association of

Holail, Jasmine / Mobarak, Reem / Al-Ghamdi, Bandar / Aljada, Ahmad / Fakhoury, Hana

Drug metabolism and personalized therapy

2022

Abstract: Objectives: Despite its wide usage, warfarin therapy remains challenging due to its narrow therapeutic index, inter-individual response variability, and risk of bleeding. Previous reports have suggested that polymorphisms in : Methods: This cross- ... ...

Abstract	Objectives: Despite its wide usage, warfarin therapy remains challenging due to its narrow therapeutic index, inter-individual response variability, and risk of bleeding. Previous reports have suggested that polymorphisms in Methods: This cross-sectional study was conducted on Saudi adults receiving warfarin for more than 1 month. Their demographics and relevant clinical data were obtained. Genotyping for Results: Patients who are homozygous for the mutant T allele Conclusions: Similar to other populations, the
Language	English
Publishing date	2022-04-04
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2822040-7
ISSN	2363-8915 ; 2363-8907
ISSN (online)	2363-8915
ISSN	2363-8907
DOI	10.1515/dmdi-2022-0108
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Article ; Online: Association of

Holail, Jasmine / Mobarak, Reem / Al-Ghamdi, Bandar / Aljada, Ahmad / Fakhoury, Hana

Drug metabolism and personalized therapy

2022 Volume 37, Issue 4, Page(s) 353–359

Abstract	Objectives: Despite its wide usage, warfarin therapy remains challenging due to its narrow therapeutic index, inter-individual response variability, and risk of bleeding. Previous reports have suggested that polymorphisms in Methods: This cross-sectional study was conducted on Saudi adults receiving warfarin for more than 1 month. Their demographics and relevant clinical data were obtained. Genotyping for Results: Patients who are homozygous for the mutant T allele Conclusions: Similar to other populations, the
MeSH term(s)	Humans ; Warfarin/adverse effects ; Polymorphism, Single Nucleotide/genetics ; Cross-Sectional Studies ; Cytochrome P-450 CYP2C9/genetics ; Vitamin K Epoxide Reductases/genetics
Chemical Substances	Warfarin (5Q7ZVV76EI) ; CYP2C9 protein, human (EC 1.14.13.-) ; Cytochrome P-450 CYP2C9 (EC 1.14.13.-) ; VKORC1 protein, human (EC 1.17.4.4) ; Vitamin K Epoxide Reductases (EC 1.17.4.4)
Language	English
Publishing date	2022-04-04
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2822040-7
ISSN	2363-8915 ; 2363-8907
ISSN (online)	2363-8915
ISSN	2363-8907
DOI	10.1515/dmpt-2022-0108
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Article ; Online: Differential Gene Expression Signatures and Cellular Signaling Pathways induced by Lamin A/C Transcript Variants in MCF7 Cell Line.

Batha, Lin / Aziz, Mohammad Azhar / Zhra, Mahmoud / Holail, Jasmine / Al-Qahtani, Wedad S / Fakhoury, Rajaa / Aljada, Ahmad

Frontiers in bioscience (Landmark edition)

2023 Volume 28, Issue 6, Page(s) 113

Abstract: Background: Lamins are the major component of nuclear lamina. Alternative splicing of the 12 exons comprising : Methods: Ion AmpliSeq Transcriptome Human Gene Expression analysis was performed on MCF7 cells stably transfected with lamin A/C ... ...

Abstract	Background: Lamins are the major component of nuclear lamina. Alternative splicing of the 12 exons comprising Methods: Ion AmpliSeq Transcriptome Human Gene Expression analysis was performed on MCF7 cells stably transfected with lamin A/C transcript variants. Results: Lamin A or lamin AΔ50 upregulation was associated with activation of cell death and inactivation of carcinogenesis while both lamin C or lamin AΔ10 upregulation activated carcinogenesis and cell death. Conclusions: Data suggest anti-apoptotic and anti-senescence effects of lamin C and lamin AΔ10 as several functions, including apoptosis and necrosis functions are inactivated following lamin C or lamin AΔ10 upregulation. However, lamin AΔ10 upregulation is associated with a more carcinogenic and aggressive tumor phenotype. Lamin A or lamin AΔ50 upregulation is associated with a predicted activation of increased cell death and inactivation of carcinogenesis. Thus, different signaling pathways, networks, molecular and cellular functions are activated/inactivated by lamin A/C transcript variants resulting in a large number of laminopathies.
MeSH term(s)	Humans ; Alternative Splicing ; Lamin Type A/genetics ; Lamin Type A/metabolism ; MCF-7 Cells ; Signal Transduction/genetics ; Transcriptome
Chemical Substances	Lamin Type A ; LMNA protein, human
Language	English
Publishing date	2023-07-06
Publishing country	Singapore
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2704569-9
ISSN	2768-6698 ; 2768-6698
ISSN (online)	2768-6698
ISSN	2768-6698
DOI	10.31083/j.fbl2806113
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Article ; Online: Insulin Receptor Isoforms and Insulin Growth Factor-like Receptors: Implications in Cell Signaling, Carcinogenesis, and Chemoresistance.

Galal, Mariam Ahmed / Alouch, Samhar Samer / Alsultan, Buthainah Saad / Dahman, Huda / Alyabis, Nouf Abdullah / Alammar, Sarah Ammar / Aljada, Ahmad

International journal of molecular sciences

2023 Volume 24, Issue 19

Abstract: This comprehensive review thoroughly explores the intricate involvement of insulin receptor (IR) isoforms and insulin-like growth factor receptors (IGFRs) in the context of the insulin and insulin-like growth factor (IGF) signaling (IIS) pathway. This ... ...

Abstract	This comprehensive review thoroughly explores the intricate involvement of insulin receptor (IR) isoforms and insulin-like growth factor receptors (IGFRs) in the context of the insulin and insulin-like growth factor (IGF) signaling (IIS) pathway. This elaborate system encompasses ligands, receptors, and binding proteins, giving rise to a wide array of functions, including aspects such as carcinogenesis and chemoresistance. Detailed genetic analysis of IR and IGFR structures highlights their distinct isoforms, which arise from alternative splicing and exhibit diverse affinities for ligands. Notably, the overexpression of the IR-A isoform is linked to cancer stemness, tumor development, and resistance to targeted therapies. Similarly, elevated IGFR expression accelerates tumor progression and fosters chemoresistance. The review underscores the intricate interplay between IRs and IGFRs, contributing to resistance against anti-IGFR drugs. Consequently, the dual targeting of both receptors could present a more effective strategy for surmounting chemoresistance. To conclude, this review brings to light the pivotal roles played by IRs and IGFRs in cellular signaling, carcinogenesis, and therapy resistance. By precisely modulating these receptors and their complex signaling pathways, the potential emerges for developing enhanced anti-cancer interventions, ultimately leading to improved patient outcomes.
MeSH term(s)	Humans ; Insulin/metabolism ; Receptor, Insulin/metabolism ; Drug Resistance, Neoplasm/genetics ; Receptor, IGF Type 1/genetics ; Receptor, IGF Type 1/metabolism ; Signal Transduction ; Protein Isoforms/genetics ; Protein Isoforms/metabolism ; Insulin, Regular, Human ; Neoplasms/drug therapy ; Neoplasms/genetics ; Neoplasms/metabolism ; Somatomedins ; Carcinogenesis/genetics ; Insulin-Like Growth Factor I/metabolism
Chemical Substances	Insulin ; Receptor, Insulin (EC 2.7.10.1) ; Receptor, IGF Type 1 (EC 2.7.10.1) ; Protein Isoforms ; Insulin, Regular, Human ; Somatomedins ; Insulin-Like Growth Factor I (67763-96-6)
Language	English
Publishing date	2023-10-09
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms241915006
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Article ; Online: Gene Expression Profiling of Peripheral Blood Mononuclear Cells in Type 2 Diabetes: An Exploratory Study.

Fakhoury, Hana M A / Elahi, Muhammad Affan / Al Sarheed, Saud / Al Dubayee, Mohammed / Alshahrani, Awad / Zhra, Mahmoud / Almassri, Arwa / Aljada, Ahmad

Medicina (Kaunas, Lithuania)

2022 Volume 58, Issue 12

Abstract: Background and ... ...

Abstract	Background and Objectives
Language	English
Publishing date	2022-12-12
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2188113-3
ISSN	1648-9144 ; 1010-660X
ISSN (online)	1648-9144
ISSN	1010-660X
DOI	10.3390/medicina58121829
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Article ; Online: Absolute quantification of senescence mediators in cells using multiple reaction monitoring liquid chromatography-Tandem mass spectrometry.

Galal, Mariam Ahmed / Abdel Jabar, Mai / Zhra, Mahmoud / Abdel Rahman, Anas M / Aljada, Ahmad

Analytica chimica acta

2021 Volume 1184, Page(s) 339009

Abstract: Background: The identification of unique senescence markers remains challenging. Current hallmarks of senescent cells, including increased senescence-associated β-galactosidase activity, increased levels of cell cycle regulators such as p16: ... ...

Abstract	Background: The identification of unique senescence markers remains challenging. Current hallmarks of senescent cells, including increased senescence-associated β-galactosidase activity, increased levels of cell cycle regulators such as p16 Objectives: To develop multiple reaction monitoring-based tandem mass spectrometric senescence assay for simultaneous measuring of p16 Methodology: Multiple reaction monitoring-tandem mass transitions per protein were developed for each signature peptide(s) and stable isotope-labeled internal standard. The developed assay was validated in a matrix using breast cancer MCF7 cell lines according to the US-FDA guidelines for bioanalytical assays. Results: The analytes chromatographic peaks were baseline separated and showed linear behavior in a wide dynamic range with r Conclusion: LC-MS/MS is a potent alternative tool to the currently available assays. The high throughput method established can study senescence's role in different pathophysiological processes.
MeSH term(s)	Chromatography, Liquid ; Humans ; MCF-7 Cells ; Reproducibility of Results ; Tandem Mass Spectrometry
Language	English
Publishing date	2021-09-02
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1483436-4
ISSN	1873-4324 ; 0003-2670
ISSN (online)	1873-4324
ISSN	0003-2670
DOI	10.1016/j.aca.2021.339009
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Article: Proteomic Profiling Identifies Distinct Regulation of Proteins in Obese Diabetic Patients Treated with Metformin.

Alshahrani, Awad / Aljada, Ahmad / Masood, Afshan / Mujammami, Muhammad / Alfadda, Assim A / Musambil, Mohthash / Alanazi, Ibrahim O / Al Dubayee, Mohammed / Abdel Rahman, Anas M / Benabdelkamel, Hicham

Pharmaceuticals (Basel, Switzerland)

2023 Volume 16, Issue 10

Abstract: ... ...

Abstract	Background
Language	English
Publishing date	2023-09-23
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2193542-7
ISSN	1424-8247
ISSN	1424-8247
DOI	10.3390/ph16101345
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