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1
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Hâncu IM, Giuchici S, Furdui-Lința AV, Lolescu B, Sturza A, Muntean DM, Dănilă MD, Lighezan R. The highs and lows of monoamine oxidase as molecular target in cancer: an updated review. Mol Cell Biochem 2025; 480:3225-3252. [PMID: 39714760 PMCID: PMC12095387 DOI: 10.1007/s11010-024-05192-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2024] [Accepted: 12/09/2024] [Indexed: 12/24/2024]
Abstract
The global burden of cancer as a major cause of death and invalidity has been constantly increasing in the past decades. Monoamine oxidases (MAO) with two isoforms, MAO-A and MAO-B, are mammalian mitochondrial enzymes responsible for the oxidative deamination of neurotransmitters and amines in the central nervous system and peripheral tissues with the constant generation of hydrogen peroxide as the main deleterious ancillary product. However, given the complexity of cancer biology, MAO involvement in tumorigenesis is multifaceted with different tumors displaying either an increased or decreased MAO profile. MAO inhibitors are currently approved for the treatment of neurodegenerative diseases (mainly, Parkinson's disease) and as secondary/adjunctive therapeutic options for the treatment of major depression. Herein, we review the literature characterizing MAO's involvement and the putative role of MAO inhibitors in several malignancies, and also provide perspectives regarding the potential biomarker role that MAO could play in the future in oncology.
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Affiliation(s)
- Iasmina M Hâncu
- Doctoral School of Medicine, "Victor Babeș" University of Medicine and Pharmacy of Timișoara, Timișoara, Romania
- Department III Functional Sciences-Pathophysiology, "Victor Babeș" University of Medicine and Pharmacy of Timișoara, Eftimie Murgu Sq., no.2, 300041, Timișoara, Romania
- Centre for Translational Research and Systems Medicine, "Victor Babeș" University of Medicine and Pharmacy of Timișoara, Timișoara, Romania
| | - Silvia Giuchici
- Doctoral School of Medicine, "Victor Babeș" University of Medicine and Pharmacy of Timișoara, Timișoara, Romania
- Department III Functional Sciences-Pathophysiology, "Victor Babeș" University of Medicine and Pharmacy of Timișoara, Eftimie Murgu Sq., no.2, 300041, Timișoara, Romania
- Centre for Translational Research and Systems Medicine, "Victor Babeș" University of Medicine and Pharmacy of Timișoara, Timișoara, Romania
| | - Adina V Furdui-Lința
- Doctoral School of Medicine, "Victor Babeș" University of Medicine and Pharmacy of Timișoara, Timișoara, Romania
- Department III Functional Sciences-Pathophysiology, "Victor Babeș" University of Medicine and Pharmacy of Timișoara, Eftimie Murgu Sq., no.2, 300041, Timișoara, Romania
- Centre for Translational Research and Systems Medicine, "Victor Babeș" University of Medicine and Pharmacy of Timișoara, Timișoara, Romania
| | - Bogdan Lolescu
- Doctoral School of Medicine, "Victor Babeș" University of Medicine and Pharmacy of Timișoara, Timișoara, Romania
- Centre for Translational Research and Systems Medicine, "Victor Babeș" University of Medicine and Pharmacy of Timișoara, Timișoara, Romania
| | - Adrian Sturza
- Department III Functional Sciences-Pathophysiology, "Victor Babeș" University of Medicine and Pharmacy of Timișoara, Eftimie Murgu Sq., no.2, 300041, Timișoara, Romania
- Centre for Translational Research and Systems Medicine, "Victor Babeș" University of Medicine and Pharmacy of Timișoara, Timișoara, Romania
| | - Danina M Muntean
- Department III Functional Sciences-Pathophysiology, "Victor Babeș" University of Medicine and Pharmacy of Timișoara, Eftimie Murgu Sq., no.2, 300041, Timișoara, Romania
- Centre for Translational Research and Systems Medicine, "Victor Babeș" University of Medicine and Pharmacy of Timișoara, Timișoara, Romania
| | - Maria D Dănilă
- Department III Functional Sciences-Pathophysiology, "Victor Babeș" University of Medicine and Pharmacy of Timișoara, Eftimie Murgu Sq., no.2, 300041, Timișoara, Romania.
- Centre for Translational Research and Systems Medicine, "Victor Babeș" University of Medicine and Pharmacy of Timișoara, Timișoara, Romania.
| | - Rodica Lighezan
- Department XIII Infectious Diseases-Parasitology, "Victor Babeș" University of Medicine and Pharmacy of Timișoara, Timișoara, Romania
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2
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Morales-Montesinos IB, Rios MY, Ocampo-Acuña YD, Esquivel-Rodríguez B, Bustos-Brito C, Osorio-Ramírez MDC, Durán-Riveroll LM, González-Maya L. The Benthic Dinoflagellate Coolia malayensis (Dinophyceae) Produces an Array of Compounds with Antineoplastic Activity in Cells of Tumor Origin. Mar Drugs 2025; 23:127. [PMID: 40137313 PMCID: PMC11944075 DOI: 10.3390/md23030127] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2025] [Revised: 03/10/2025] [Accepted: 03/12/2025] [Indexed: 03/27/2025] Open
Abstract
Among aquatic organisms, marine dinoflagellates are essential sources of bioactive metabolites. The benthic dinoflagellate Coolia malayensis produces metabolites that have exhibited substantial and specific cytotoxicity on cancer cells; however, isolation and identification of the purified compounds remain a challenge. This study reports C. malayensis biomass multi-step extraction plus chemical analyses for identifying compounds with antineoplastic activity. Through bio-directed fractionation, the cytotoxicity of extracts and fractions was tested on H1299 (lung), PC-3 (prostate), HeLa (cervical), and MCF-7 (breast) cancer cell lines. Dichloromethane (DCM) phase, hydroalcoholic (HYD) secondary extract, and methanolic (MET) extract showed cytotoxic effects on all cell lines. Active extracts and fractions were analyzed by HPLC-QTOF-MS, 1H, and 13C NMR. Cell lines H1299 and PC-3 treated with fractions F4, F7, and DCM2-AQ-Ch sub-extract showed morphological changes resembling those observed in the apoptosis control, and no signs of necrosis were observed. The selectivity of fraction F7 was above 100 μg mL-1 for healthy cells, while cytotoxic activity was observed in cancer cells. This fraction was identified as mostly fatty acids (FA) by NMR. Seventeen compounds with reported biological activities, such as antioxidant, analgesic, antiviral, and anticancer, were identified from C. malayensis extracts and fractions. Among them, the phycotoxins gambieric acid A and B, okadaic acid, and dinophysistoxin-1 were detected. Further studies are needed to reveal more significant anti-cancer potential from C. malayensis.
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Affiliation(s)
- Itzel B. Morales-Montesinos
- Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Av. Universidad 1001, Col. Chamilpa, Cuernavaca 62209, Mexico;
| | - Maria Yolanda Rios
- Centro de Investigaciones Químicas, IICBA, Universidad Autónoma del Estado de Morelos, Av. Universidad 1001, Col. Chamilpa, Cuernavaca 62209, Mexico; (M.Y.R.); (Y.D.O.-A.)
| | - Yordin D. Ocampo-Acuña
- Centro de Investigaciones Químicas, IICBA, Universidad Autónoma del Estado de Morelos, Av. Universidad 1001, Col. Chamilpa, Cuernavaca 62209, Mexico; (M.Y.R.); (Y.D.O.-A.)
| | - Baldomero Esquivel-Rodríguez
- Instituto de Química, Universidad Nacional Autónoma de México, Circuito Exterior, Ciudad Universitaria, Mexico City 04510, Mexico; (B.E.-R.); (C.B.-B.)
| | - Celia Bustos-Brito
- Instituto de Química, Universidad Nacional Autónoma de México, Circuito Exterior, Ciudad Universitaria, Mexico City 04510, Mexico; (B.E.-R.); (C.B.-B.)
| | - María del Carmen Osorio-Ramírez
- Departamento de Biotecnología Marina, Centro de Investigación Científica y de Educación Superior de Ensenada, Ensenada 22860, Mexico;
| | - Lorena M. Durán-Riveroll
- SECIHTI-Departamento de Biotecnología Marina, Centro de Investigación Científica y de Educación, Superior de Ensenada, Ensenada 22860, Mexico
| | - Leticia González-Maya
- Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Av. Universidad 1001, Col. Chamilpa, Cuernavaca 62209, Mexico;
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Shen X, Miao S, Zhang Y, Guo X, Li W, Mao X, Zhang Q. Stearic acid metabolism in human health and disease. Clin Nutr 2025; 44:222-238. [PMID: 39709650 DOI: 10.1016/j.clnu.2024.12.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Revised: 11/25/2024] [Accepted: 12/07/2024] [Indexed: 12/24/2024]
Abstract
Named after the Greek term for "hard fat", stearic acid has gradually entered people's field of vision. As an important component of various physiological cellular functions, stearic acid plays a regulatory role in diverse aspects of energy metabolism and signal transduction. Its applications range from serving as a bodily energy source to participating in endogenous biosynthesis. Similar to palmitate, stearic acid serves as a primary substrate for the stearoyl coenzyme A desaturase, which catalyzes the conversion of stearate to oleate and is involved in the synthesis of triglyceride and other complex lipids. Additionally, stearic acid functions as a vital signaling molecule in pathological processes such as cardiovascular diseases, diabetes development, liver injury and even nervous system disorders. Therefore, we conduct a comprehensive review of stearic acid, summarizing its role in various diseases and attempting to provide a systematic overview of its homeostasis, physiological functions, and pathological process. From a medical standpoint, we also explore potential applications and discuss stearic acid as a potential therapeutic target for the treatment of human diseases.
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Affiliation(s)
- Xinyi Shen
- Department of Urology, Affiliated Hospital of Qingdao University, Qingdao, China; School of Basic Medicine, Qingdao University, Qingdao, China
| | - Shuo Miao
- School of Basic Medicine, Qingdao University, Qingdao, China
| | - Yaping Zhang
- Department of Operating Room, Affiliated Hospital of Qingdao University, Qingdao, China
| | - Xingying Guo
- Department of Operating Room, Affiliated Hospital of Qingdao University, Qingdao, China
| | - Wenxian Li
- Department of Urology, Affiliated Hospital of Qingdao University, Qingdao, China
| | - Xin Mao
- Department of Urology, Affiliated Hospital of Qingdao University, Qingdao, China.
| | - Qingsong Zhang
- Department of Urology, Affiliated Hospital of Qingdao University, Qingdao, China.
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4
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Fine H, Bonthu A, Kogan M. Integrative Geriatric Oncology: A Review of Current Practices. Curr Oncol Rep 2024; 26:1146-1158. [PMID: 39042197 DOI: 10.1007/s11912-024-01575-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/29/2024] [Indexed: 07/24/2024]
Abstract
PURPOSE OF REVIEW This article aims to offer a comprehensive review of optimal integrative medicine practices for geriatric oncology patients. Given the aging population and the global rise in cancer incidence, it is crucial to identify evidence-based modalities and employ an integrated approach to enhance cancer outcomes and quality of life in older adults. RECENT FINDINGS It has been predicted that 20.5% (6.9 million) of new cancer cases in 2050 will occur in adults over 80 years old.1 The increasing focus on lifestyle factors in healthy aging has shed light on various overlooked areas of significance. Notably, anti-inflammatory diets and the promotion of a healthy gut microbiome have demonstrated significant impacts on overall health outcomes, bolstering the body's innate capacity to combat disease. This review delves into further evidence and extrapolation concerning integrative approaches and their influence on cancer outcomes and older adults quality of life. The complexity and unique nature of cancer in older adults requires a wide range of support from medical providers. Incorporating various integrative techniques as part of cancer treatment and side effect support can improve health outcomes and patient's quality of life. Familiarity with the lifestyle interventions and other topics explored in this review equips healthcare providers to offer tailored and holistic care to geriatric patients navigating cancer.
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Affiliation(s)
- Hannah Fine
- GW Center for Integrative Medicine, GW University, Washington, D.C, USA
| | - Amrita Bonthu
- Georgetown University Masters in Integrative Medicine and Health Sciences, Washington, D.C, USA
| | - Mikhail Kogan
- GW Center for Integrative Medicine, GW University, Washington, D.C, USA.
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5
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Bardaweel SK, Al-salamat H, Hajjo R, Sabbah D, Almutairi S. Unveiling the Intricacies of Monoamine Oxidase-A (MAO-A) Inhibition in Colorectal Cancer: Computational Systems Biology, Expression Patterns, and the Anticancer Therapeutic Potential. ACS OMEGA 2024; 9:35703-35717. [PMID: 39184489 PMCID: PMC11339988 DOI: 10.1021/acsomega.4c04100] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Revised: 07/24/2024] [Accepted: 07/26/2024] [Indexed: 08/27/2024]
Abstract
Colorectal cancer (CRC) remains a significant health burden globally, necessitating a deeper understanding of its molecular intricacies for effective therapeutic interventions. Elevated monoamine oxidase-A (MAO-A) expression has been consistently observed in CRC tissues, correlating with advanced disease stages and a poorer prognosis. This research explores the systems biology effects of MAO-A inhibition with small molecule inhibitor clorgyline regarding CRC. The applied systems biology approach starts with a chemocentric informatics approach to derive high-confidence hypotheses regarding the antiproliferative effects of MAO-A inhibitors and ends with experimental validation. Our computational results emphasized the anticancer effects of MAO-A inhibition and the chemogenomics similarities between clorgyline and structurally diverse groups of apoptosis inducers in addition to highlighting apoptotic, DNA-damage, and microRNAs in cancer pathways. Experimental validation results revealed that MAO inhibition results in antiproliferative antimigratory activities in addition to synergistic effects with doxorubicin. Moreover, the results demonstrated a putative role of MAO-A inhibition in commencing CRC cellular death by potentially mediating the induction of apoptosis.
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Affiliation(s)
- Sanaa K. Bardaweel
- Department
of Pharmaceutical Sciences, School of Pharmacy, The University of Jordan, Amman - 11942, Jordan
| | - Husam Al-salamat
- Department
of Pharmaceutical Sciences, School of Pharmacy, The University of Jordan, Amman - 11942, Jordan
| | - Rima Hajjo
- Department
of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah
University of Jordan, P.O. Box 130, Amman - 11733, Jordan
- Laboratory
for Molecular Modeling, Division of Chemical Biology and Medicinal
Chemistry, Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States
- Board
Member, Jordan CDC, Amman - 11183, Jordan
| | - Dima Sabbah
- Department
of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah
University of Jordan, P.O. Box 130, Amman - 11733, Jordan
| | - Shriefa Almutairi
- Department
of Pharmaceutical Sciences, School of Pharmacy, The University of Jordan, Amman - 11942, Jordan
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Lukasiewicz M, Zwara A, Kowalski J, Mika A, Hellmann A. The Role of Lipid Metabolism Disorders in the Development of Thyroid Cancer. Int J Mol Sci 2024; 25:7129. [PMID: 39000236 PMCID: PMC11241618 DOI: 10.3390/ijms25137129] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2024] [Revised: 06/21/2024] [Accepted: 06/25/2024] [Indexed: 07/16/2024] Open
Abstract
Thyroid cancer (TC) is a neoplasm with an increasing incidence worldwide. Its etiology is complex and based on a multi-layered interplay of factors. Among these, disorders of lipid metabolism have emerged as an important area of investigation. Cancer cells are metabolically reprogrammed to promote their rapid growth, proliferation, and survival. This reprogramming is associated with significant changes at the level of lipids, mainly fatty acids (FA), as they play a critical role in maintaining cell structure, facilitating signaling pathways, and providing energy. These lipid-related changes help cancer cells meet the increased demands of continued growth and division while adapting to the tumor microenvironment. In this review, we examine lipid metabolism at different stages, including synthesis, transport, and oxidation, in the context of TC and the effects of obesity and hormones on TC development. Recent scientific efforts have revealed disturbances in lipid homeostasis that are specific to thyroid cancer, opening up potential avenues for early detection and targeted therapeutic interventions. Understanding the intricate metabolic pathways involved in FA metabolism may provide insights into potential interventions to prevent cancer progression and mitigate its effects on surrounding tissues.
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Affiliation(s)
- Martyna Lukasiewicz
- Department of General, Endocrine and Transplant Surgery, Faculty of Medicine, Medical University of Gdansk, 80-211 Gdansk, Poland
| | - Agata Zwara
- Department of Environmental Analytics, Faculty of Chemistry, University of Gdansk, 80-309 Gdansk, Poland
| | - Jacek Kowalski
- Department of Pathomorphology, Faculty of Medicine, Medical University of Gdansk, 80-211 Gdansk, Poland
- International Centre for Cancer Vaccine Science, University of Gdansk, 80-309 Gdansk, Poland
| | - Adriana Mika
- Department of Environmental Analytics, Faculty of Chemistry, University of Gdansk, 80-309 Gdansk, Poland
- Department of Pharmaceutical Biochemistry, Medical University of Gdansk, 80-211 Gdansk, Poland
| | - Andrzej Hellmann
- Department of General, Endocrine and Transplant Surgery, Faculty of Medicine, Medical University of Gdansk, 80-211 Gdansk, Poland
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7
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Al-Rashed F, Arefanian H, Madhoun AA, Bahman F, Sindhu S, AlSaeed H, Jacob T, Thomas R, Al-Roub A, Alzaid F, Malik MDZ, Nizam R, Thanaraj TA, Al-Mulla F, Hannun YA, Ahmad R. Neutral Sphingomyelinase 2 Inhibition Limits Hepatic Steatosis and Inflammation. Cells 2024; 13:463. [PMID: 38474427 PMCID: PMC10931069 DOI: 10.3390/cells13050463] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2024] [Revised: 02/29/2024] [Accepted: 03/03/2024] [Indexed: 03/14/2024] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is manifested by hepatic steatosis, insulin resistance, hepatocyte death, and systemic inflammation. Obesity induces steatosis and chronic inflammation in the liver. However, the precise mechanism underlying hepatic steatosis in the setting of obesity remains unclear. Here, we report studies that address this question. After 14 weeks on a high-fat diet (HFD) with high sucrose, C57BL/6 mice revealed a phenotype of liver steatosis. Transcriptional profiling analysis of the liver tissues was performed using RNA sequencing (RNA-seq). Our RNA-seq data revealed 692 differentially expressed genes involved in processes of lipid metabolism, oxidative stress, immune responses, and cell proliferation. Notably, the gene encoding neutral sphingomyelinase, SMPD3, was predominantly upregulated in the liver tissues of the mice displaying a phenotype of steatosis. Moreover, nSMase2 activity was elevated in these tissues of the liver. Pharmacological and genetic inhibition of nSMase2 prevented intracellular lipid accumulation and TNFα-induced inflammation in in-vitro HepG2-steatosis cellular model. Furthermore, nSMase2 inhibition ameliorates oxidative damage by rescuing PPARα and preventing cell death associated with high glucose/oleic acid-induced fat accumulation in HepG2 cells. Collectively, our findings highlight the prominent role of nSMase2 in hepatic steatosis, which could serve as a potential therapeutic target for NAFLD and other hepatic steatosis-linked disorders.
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Affiliation(s)
- Fatema Al-Rashed
- Immunology & Microbiology Department, Dasman Diabetes Institute, Dasman 15462, Kuwait; (H.A.); (F.B.); (H.A.); (T.J.); (R.T.); (A.A.-R.)
| | - Hossein Arefanian
- Immunology & Microbiology Department, Dasman Diabetes Institute, Dasman 15462, Kuwait; (H.A.); (F.B.); (H.A.); (T.J.); (R.T.); (A.A.-R.)
| | - Ashraf Al Madhoun
- Animal and Imaging Core Facilities, Dasman Diabetes Institute, Dasman 15462, Kuwait; (A.A.M.); (S.S.)
| | - Fatemah Bahman
- Immunology & Microbiology Department, Dasman Diabetes Institute, Dasman 15462, Kuwait; (H.A.); (F.B.); (H.A.); (T.J.); (R.T.); (A.A.-R.)
| | - Sardar Sindhu
- Animal and Imaging Core Facilities, Dasman Diabetes Institute, Dasman 15462, Kuwait; (A.A.M.); (S.S.)
| | - Halemah AlSaeed
- Immunology & Microbiology Department, Dasman Diabetes Institute, Dasman 15462, Kuwait; (H.A.); (F.B.); (H.A.); (T.J.); (R.T.); (A.A.-R.)
| | - Texy Jacob
- Immunology & Microbiology Department, Dasman Diabetes Institute, Dasman 15462, Kuwait; (H.A.); (F.B.); (H.A.); (T.J.); (R.T.); (A.A.-R.)
| | - Reeby Thomas
- Immunology & Microbiology Department, Dasman Diabetes Institute, Dasman 15462, Kuwait; (H.A.); (F.B.); (H.A.); (T.J.); (R.T.); (A.A.-R.)
| | - Areej Al-Roub
- Immunology & Microbiology Department, Dasman Diabetes Institute, Dasman 15462, Kuwait; (H.A.); (F.B.); (H.A.); (T.J.); (R.T.); (A.A.-R.)
| | - Fawaz Alzaid
- Université Paris Cité, INSERM UMR-S1151, CNRS UMR-S8253, Institut Necker Enfants Malades, F-75015 Paris, France;
| | - MD Zubbair Malik
- Genetics and Bioinformatics Department, Dasman Diabetes Institute, Dasman 15462, Kuwait; (M.Z.M.); (R.N.); (T.A.T.); (F.A.-M.)
| | - Rasheeba Nizam
- Genetics and Bioinformatics Department, Dasman Diabetes Institute, Dasman 15462, Kuwait; (M.Z.M.); (R.N.); (T.A.T.); (F.A.-M.)
| | - Thangavel Alphonse Thanaraj
- Genetics and Bioinformatics Department, Dasman Diabetes Institute, Dasman 15462, Kuwait; (M.Z.M.); (R.N.); (T.A.T.); (F.A.-M.)
| | - Fahd Al-Mulla
- Genetics and Bioinformatics Department, Dasman Diabetes Institute, Dasman 15462, Kuwait; (M.Z.M.); (R.N.); (T.A.T.); (F.A.-M.)
| | - Yusuf A. Hannun
- Stony Brook Cancer Center, Stony Brook University, Stony Brook, NY 11794, USA;
| | - Rasheed Ahmad
- Immunology & Microbiology Department, Dasman Diabetes Institute, Dasman 15462, Kuwait; (H.A.); (F.B.); (H.A.); (T.J.); (R.T.); (A.A.-R.)
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Sblano S, Boccarelli A, Mesiti F, Purgatorio R, de Candia M, Catto M, Altomare CD. A second life for MAO inhibitors? From CNS diseases to anticancer therapy. Eur J Med Chem 2024; 267:116180. [PMID: 38290352 DOI: 10.1016/j.ejmech.2024.116180] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2023] [Revised: 01/22/2024] [Accepted: 01/23/2024] [Indexed: 02/01/2024]
Abstract
Monoamine oxidases A and B (MAO A, B) are ubiquitous enzymes responsible for oxidative deamination of amine neurotransmitters and xenobiotics. Despite decades of studies, MAO inhibitors (MAOIs) find today limited therapeutic space as second-line drugs for the treatment of depression and Parkinson's disease. In recent years, a renewed interest in MAOIs has been raised up by several studies investigating the role of MAOs, particularly MAO A, in tumor insurgence and progression, and the efficacy of MAOIs as coadjutants in the therapy of chemoresistant tumors. In this survey, we highlight the implication of MAOs in the biochemical pathways of tumorigenesis and review the state-of-the-art of preclinical and clinical studies of MAOIs as anticancer agents used in monotherapy or in combination with antitumor chemotherapeutics.
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Affiliation(s)
- Sabina Sblano
- Department of Pharmacy-Pharmaceutical Sciences, University of Bari Aldo Moro, Via E. Orabona 4, 70125, Bari, Italy
| | - Angelina Boccarelli
- Department of Precision and Regenerative Medicine and Ionian Area, School of Medicine, University of Bari Aldo Moro, Piazza Giulio Cesare 11, 70124, Bari, Italy.
| | - Francesco Mesiti
- Department of Pharmacy-Pharmaceutical Sciences, University of Bari Aldo Moro, Via E. Orabona 4, 70125, Bari, Italy
| | - Rosa Purgatorio
- Department of Pharmacy-Pharmaceutical Sciences, University of Bari Aldo Moro, Via E. Orabona 4, 70125, Bari, Italy
| | - Modesto de Candia
- Department of Pharmacy-Pharmaceutical Sciences, University of Bari Aldo Moro, Via E. Orabona 4, 70125, Bari, Italy
| | - Marco Catto
- Department of Pharmacy-Pharmaceutical Sciences, University of Bari Aldo Moro, Via E. Orabona 4, 70125, Bari, Italy.
| | - Cosimo D Altomare
- Department of Pharmacy-Pharmaceutical Sciences, University of Bari Aldo Moro, Via E. Orabona 4, 70125, Bari, Italy
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9
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Panchali T, Dutta A, Das P, Khatun A, Kar R, Mondal S, Mondal KC, Chakrabarti S, Ghosh K, Pradhan S. Amelioration of obesity induction by a high-fat diet and related inflammation by Phasa fish (Setipinna phasa) oil in BALB/c mice. J Appl Biomed 2024; 22:49-58. [PMID: 38505970 DOI: 10.32725/jab.2024.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2022] [Accepted: 01/31/2024] [Indexed: 03/21/2024] Open
Abstract
We have extracted and characterized Phasa fish (Setipinna phasa) oil for the first time to evaluate the anti-obesity and related anti-inflammatory effects on obese mice. Inbred male albino BALB/c mice were segregated into three categories: control (C), Obese control group (OC), and Phasa fish oil treated group (TX). To establish the potentiality of Setipinna phasa oil for its anti-obesity and anti-inflammatory properties, it was extracted and characterized using GC-MS method. To evaluate the anti-obesity effect, different parameters were considered, such as body weight, lipid composition, obesity, and obesity associated inflammation. The physicochemical characteristics of Phasa fish oil revealed that the oil quality was good because acid value, peroxide value, p-anisidine value, Totox value, refractive index, and saponification value were within the standard value range. The GC-MS study explored the presence of fatty acids beneficial to health such as Hexadec-9-enoic acid; Octadec-11-enoic acid; EPA, DHA, Methyl Linolenate, etc. The application of Setipinna phasa oil on the treated mice group acutely lowered body weight and serum lipid profile compared to the obese group. In connection with this, leptin, FAS, and pro-inflammatory cytokines TNF-α genes expression were downregulated in the treated group compared to the obese group. The Phasa oil treated group had an elevated expression of PPAR-α, adiponectin, LPL gene, and anti-inflammatory markers IL-10 and IL-1Ra compared to the obese group. This study suggests that Phasa fish oil, enriched with essential fatty acid, might be used as an anti-obesity and anti-inflammatory supplement.
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Affiliation(s)
- Titli Panchali
- Midnapore City College, Department of Paramedical and Allied Health Sciences, Bhadutala, Paschim Medinipur, West Bengal, India
| | - Ananya Dutta
- Midnapore City College, Department of Paramedical and Allied Health Sciences, Bhadutala, Paschim Medinipur, West Bengal, India
| | - Pipika Das
- Midnapore City College, Department of Paramedical and Allied Health Sciences, Bhadutala, Paschim Medinipur, West Bengal, India
| | - Amina Khatun
- Midnapore City College, Department of Paramedical and Allied Health Sciences, Bhadutala, Paschim Medinipur, West Bengal, India
| | - Riya Kar
- Midnapore City College, Department of Paramedical and Allied Health Sciences, Bhadutala, Paschim Medinipur, West Bengal, India
| | - Subhadeep Mondal
- Midnapore City College, Department of Paramedical and Allied Health Sciences, Bhadutala, Paschim Medinipur, West Bengal, India
| | | | - Sudipta Chakrabarti
- Midnapore City College, Department of Paramedical and Allied Health Sciences, Bhadutala, Paschim Medinipur, West Bengal, India
| | - Kuntal Ghosh
- Midnapore City College, Department of Paramedical and Allied Health Sciences, Bhadutala, Paschim Medinipur, West Bengal, India
| | - Shrabani Pradhan
- Midnapore City College, Department of Paramedical and Allied Health Sciences, Bhadutala, Paschim Medinipur, West Bengal, India
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10
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Lin Z, Long F, Kang R, Klionsky DJ, Yang M, Tang D. The lipid basis of cell death and autophagy. Autophagy 2024; 20:469-488. [PMID: 37768124 PMCID: PMC10936693 DOI: 10.1080/15548627.2023.2259732] [Citation(s) in RCA: 32] [Impact Index Per Article: 32.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2023] [Revised: 08/25/2023] [Accepted: 09/12/2023] [Indexed: 09/29/2023] Open
Abstract
ABBREVIATIONS ACSL: acyl-CoA synthetase long chain family; DISC: death-inducing signaling complex; DAMPs: danger/damage-associated molecular patterns; Dtgn: dispersed trans-Golgi network; FAR1: fatty acyl-CoA reductase 1; GPX4: glutathione peroxidase 4; LPCAT3: lysophosphatidylcholine acyltransferase 3; LPS: lipopolysaccharide; MUFAs: monounsaturated fatty acids; MOMP: mitochondrial outer membrane permeabilization; MLKL, mixed lineage kinase domain like pseudokinase; oxPAPC: oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine; OxPCs: oxidized phosphatidylcholines; PUFAs: polyunsaturated fatty acids; POR: cytochrome p450 oxidoreductase; PUFAs: polyunsaturated fatty acids; RCD: regulated cell death; RIPK1: receptor interacting serine/threonine kinase 1; SPHK1: sphingosine kinase 1; SOAT1: sterol O-acyltransferase 1; SCP2: sterol carrier protein 2; SFAs: saturated fatty acids; SLC47A1: solute carrier family 47 member 1; SCD: stearoyl-CoA desaturase; VLCFA: very long chain fatty acids.
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Affiliation(s)
- Zhi Lin
- Department of Pediatrics, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China
- Hunan Clinical Research Center of Pediatric Cancer, Changsha, Hunan, China
| | - Fei Long
- Department of Gastrointestinal Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China
- Postdoctoral Research Station of Basic Medicine, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Rui Kang
- Department of Surgery, UT Southwestern Medical Center, Dallas, TX, USA
| | - Daniel J. Klionsky
- Life Sciences Institute and Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI, USA
| | - Minghua Yang
- Department of Pediatrics, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China
- Hunan Clinical Research Center of Pediatric Cancer, Changsha, Hunan, China
| | - Daolin Tang
- Department of Surgery, UT Southwestern Medical Center, Dallas, TX, USA
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11
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Ali O, Szabó A. Review of Eukaryote Cellular Membrane Lipid Composition, with Special Attention to the Fatty Acids. Int J Mol Sci 2023; 24:15693. [PMID: 37958678 PMCID: PMC10649022 DOI: 10.3390/ijms242115693] [Citation(s) in RCA: 25] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2023] [Revised: 10/24/2023] [Accepted: 10/25/2023] [Indexed: 11/15/2023] Open
Abstract
Biological membranes, primarily composed of lipids, envelop each living cell. The intricate composition and organization of membrane lipids, including the variety of fatty acids they encompass, serve a dynamic role in sustaining cellular structural integrity and functionality. Typically, modifications in lipid composition coincide with consequential alterations in universally significant signaling pathways. Exploring the various fatty acids, which serve as the foundational building blocks of membrane lipids, provides crucial insights into the underlying mechanisms governing a myriad of cellular processes, such as membrane fluidity, protein trafficking, signal transduction, intercellular communication, and the etiology of certain metabolic disorders. Furthermore, comprehending how alterations in the lipid composition, especially concerning the fatty acid profile, either contribute to or prevent the onset of pathological conditions stands as a compelling area of research. Hence, this review aims to meticulously introduce the intricacies of membrane lipids and their constituent fatty acids in a healthy organism, thereby illuminating their remarkable diversity and profound influence on cellular function. Furthermore, this review aspires to highlight some potential therapeutic targets for various pathological conditions that may be ameliorated through dietary fatty acid supplements. The initial section of this review expounds on the eukaryotic biomembranes and their complex lipids. Subsequent sections provide insights into the synthesis, membrane incorporation, and distribution of fatty acids across various fractions of membrane lipids. The last section highlights the functional significance of membrane-associated fatty acids and their innate capacity to shape the various cellular physiological responses.
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Affiliation(s)
- Omeralfaroug Ali
- Agrobiotechnology and Precision Breeding for Food Security National Laboratory, Institute of Physiology and Animal Nutrition, Department of Animal Physiology and Health, Hungarian University of Agriculture and Life Sciences, Guba Sándor Str. 40, 7400 Kaposvár, Hungary;
| | - András Szabó
- Agrobiotechnology and Precision Breeding for Food Security National Laboratory, Institute of Physiology and Animal Nutrition, Department of Animal Physiology and Health, Hungarian University of Agriculture and Life Sciences, Guba Sándor Str. 40, 7400 Kaposvár, Hungary;
- HUN-REN-MATE Mycotoxins in the Food Chain Research Group, Hungarian University of Agriculture and Life Sciences, Guba Sándor Str. 40, 7400 Kaposvár, Hungary
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12
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Chen KQ, Lei GL, Ke BY, Chen L, Wang ZB, Wang SZ. STK25: a viable therapeutic target for cancer treatments? Anticancer Drugs 2023; 34:995-1001. [PMID: 36728989 DOI: 10.1097/cad.0000000000001490] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
Serine/threonine protein kinase 25 (STK25) is a critical regulator of ectopic lipid storage, glucose and insulin homeostasis, fibrosis, and meta-inflammation. More and more studies have revealed a strong correlation between STK25 and human diseases. On the one hand, STK25 can affect glucose and fatty acid metabolism in normal cells or tumors. On the other hand, STK25 participates in autophagy, cell polarity, cell apoptosis, and cell migration by activating various signaling pathways. This article reviews the composition and function of STK25, the energy metabolism and potential drugs that may target STK25, and the research progress of STK25 in the occurrence and development of tumors, to provide a reference for the clinical treatment of tumors.
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Affiliation(s)
- Ke-Qian Chen
- Department of Pharmacology, Institute of Pharmacy and Pharmacology, School of Pharmaceutical Sciences, Hengyang Medical School
- Department of Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, China
| | - Guan-Lan Lei
- Department of Pharmacology, Institute of Pharmacy and Pharmacology, School of Pharmaceutical Sciences, Hengyang Medical School
- Department of Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, China
| | - Bo-Yi Ke
- Department of Pharmacology, Institute of Pharmacy and Pharmacology, School of Pharmaceutical Sciences, Hengyang Medical School
- Department of Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, China
| | - Lu Chen
- Department of Pharmacology, Institute of Pharmacy and Pharmacology, School of Pharmaceutical Sciences, Hengyang Medical School
- Department of Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, China
| | - Zong-Bao Wang
- Department of Pharmacology, Institute of Pharmacy and Pharmacology, School of Pharmaceutical Sciences, Hengyang Medical School
- Department of Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, China
| | - Shu-Zhi Wang
- Department of Pharmacology, Institute of Pharmacy and Pharmacology, School of Pharmaceutical Sciences, Hengyang Medical School
- Department of Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, China
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13
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Tarai SK, Pan A, Biswas P, Bhaduri R, Mandal S, Paul A, Baitalik S, Bhattacharjee A, Moi SC. Anticancer Behavior of Pyrrolidine-Based Palladium(II) Complexes and Biophysical Approach on Their DNA, BSA Binding Activity, Molecular Docking, and DFT Study. LANGMUIR : THE ACS JOURNAL OF SURFACES AND COLLOIDS 2023; 39:10947-10964. [PMID: 37501125 DOI: 10.1021/acs.langmuir.3c01186] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/29/2023]
Abstract
A series of pyrrolidine-based Pd(II) complexes, [Pd(AEP)Cl2] (C-1), [Pd(AEP)(OH2)2]2+(C-2), [Pd(AEP)(L-cys)]+ (C-3), [Pd(AEP)(N-ac-L-cys)] (C-4), [Pd(AEP)(GSH)] (C-5), and [Pd(AEP)(DL-meth)]2+ (C-6) (where, AEP = 1-(2-aminoethyl)pyrrolidine, L-cys = l-cysteine, N-ac-L-cys = N-acetyl-l-cysteine, GSH = glutathione, and DL-meth = dl-methionine), as anticancer drug candidates have been synthesized and characterized. The DNA binding property of the complexes was executed by gel electrophoresis and spectrophotometric and viscometric methods, and their interaction with BSA was also investigated by various spectroscopic methodologies. The binding activity of the Pd(II) complexes with DNA and BSA were assessed to evaluate their binding mode and binding constants. Molecular docking was performed to correlate with the experimental results on the interaction of the complexes with DNA and BSA. The changes in the microenvironmental and structural properties of BSA are monitored by a synchronous and 3D fluorescence study. The structural properties were evaluated by DFT and TD-DFT studies. The anticarcinogenic activity of the Pd(II) complexes was assessed by PASS prediction software to corroborate with the experimental results of the anticancer activity of the complexes. The ROS generation in cancer cell lines has been investigated, and the cell death mechanism through apoptosis was confirmed by measuring the protein expression. All these complexes have excellent anticancer activity compared to ancillary ligands. The cancer cell line (HCT116) shows almost similar or better cell inhibition activity when treated with the Pd(II) complexes compared to cisplatin, whereas the adverse effect is minimum on a normal cell (NKE). Both the Pd(II) and Pt(II) complexes carrying the same ligands reveal almost similar antiproliferative activity.
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Affiliation(s)
- Swarup Kumar Tarai
- Department of Chemistry, National Institute of Technology Durgapur, Durgapur, West Bengal 713209, India
| | - Angana Pan
- Department of Chemistry, National Institute of Technology Durgapur, Durgapur, West Bengal 713209, India
| | - Pritam Biswas
- Department of Biotechnology, National Institute of Technology Durgapur, Durgapur, West Bengal 713209, India
| | - Rituparna Bhaduri
- Department of Chemistry, National Institute of Technology Durgapur, Durgapur, West Bengal 713209, India
| | - Saikat Mandal
- Department of Chemistry, National Institute of Technology Durgapur, Durgapur, West Bengal 713209, India
| | - Animesh Paul
- Inorganic Chemistry Section, Department of Chemistry, Jadavpur University, Kolkata 700032, India
| | - Sujoy Baitalik
- Inorganic Chemistry Section, Department of Chemistry, Jadavpur University, Kolkata 700032, India
| | - Ashish Bhattacharjee
- Department of Biotechnology, National Institute of Technology Durgapur, Durgapur, West Bengal 713209, India
| | - Sankar Ch Moi
- Department of Chemistry, National Institute of Technology Durgapur, Durgapur, West Bengal 713209, India
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14
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Zhang S, Jiao S, Liu D, Xie C, Dong Y, Zheng K, Liu B, Pang Q. Characterization of the lipidomic profile of clam Meretrix petechialis in response to Vibrio parahaemolyticus infection. FISH & SHELLFISH IMMUNOLOGY 2023; 134:108602. [PMID: 36758655 DOI: 10.1016/j.fsi.2023.108602] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/10/2022] [Revised: 01/25/2023] [Accepted: 02/06/2023] [Indexed: 06/18/2023]
Abstract
Vibrio parahaemolyticus is a devastating pathogen of clam Meretrix petechialis, which brings about huge economic losses in aquaculture breeding industry. In our previous study, we have found that Vibrio infection is closely associated with lipid metabolism of clams. In this study, an untargeted lipidomics approach was used to explore the lipid profiling changes upon Vibrio infection. The results demonstrated that the hepatopancreas of clams was composed of five lipid categories including fatty acyls, glycerolipids, glycerophospholipids, sphingolipids and sterol lipids. And the content of lipid classes altered during Vibrio infection, implying that Vibrio infection altered intracellular lipid homeostasis in clams. Meanwhile, a total of 200 lipid species including 82 up-regulated and 118 down-regulated significantly were identified in response to Vibrio infection, of which ceramide (Cer), phosphatidylcholine (PC) and triglyceride (TG) accounted for the largest proportion. Notably, all Cers showed a significantly decreased trend while nearly all TG species were increased significantly during Vibrio infection, which suggested that Cer and TG could be determined as effective biomarkers. Furthermore, these differentially expressed lipid species were enriched in 20 metabolic pathways and sphingolipid metabolism was one of the most enriched pathways. These results evidenced how the lipid metabolism altered in the process of Vibrio infection and opened a new perspective on the response of marine bivalves to pathogen infection.
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Affiliation(s)
- Shujing Zhang
- Anti-aging & Regenerative Medicine Research Institution, School of Life Sciences and Medicine, Shandong University of Technology, Zibo, China.
| | - Shuang Jiao
- Anti-aging & Regenerative Medicine Research Institution, School of Life Sciences and Medicine, Shandong University of Technology, Zibo, China
| | - Dongwu Liu
- Anti-aging & Regenerative Medicine Research Institution, School of Life Sciences and Medicine, Shandong University of Technology, Zibo, China
| | - Changjian Xie
- Anti-aging & Regenerative Medicine Research Institution, School of Life Sciences and Medicine, Shandong University of Technology, Zibo, China
| | - Yuling Dong
- Anti-aging & Regenerative Medicine Research Institution, School of Life Sciences and Medicine, Shandong University of Technology, Zibo, China
| | - Kang Zheng
- Anti-aging & Regenerative Medicine Research Institution, School of Life Sciences and Medicine, Shandong University of Technology, Zibo, China
| | - Baozhong Liu
- CAS Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Center for Ocean Mega-Science, Chinese Academy of Sciences, Qingdao, China
| | - Qiuxiang Pang
- Anti-aging & Regenerative Medicine Research Institution, School of Life Sciences and Medicine, Shandong University of Technology, Zibo, China.
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15
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The Landscape of Lipid Metabolism in Lung Cancer: The Role of Structural Profiling. J Clin Med 2023; 12:jcm12051736. [PMID: 36902523 PMCID: PMC10002589 DOI: 10.3390/jcm12051736] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2022] [Revised: 02/14/2023] [Accepted: 02/20/2023] [Indexed: 02/24/2023] Open
Abstract
The aim of this study was to explore the relationship between lipids with different structural features and lung cancer (LC) risk and identify prospective biomarkers of LC. Univariate and multivariate analysis methods were used to screen for differential lipids, and two machine learning methods were used to define combined lipid biomarkers. A lipid score (LS) based on lipid biomarkers was calculated, and a mediation analysis was performed. A total of 605 lipid species spanning 20 individual lipid classes were identified in the plasma lipidome. Higher carbon atoms with dihydroceramide (DCER), phosphatidylethanolamine (PE), and phosphoinositols (PI) presented a significant negative correlation with LC. Point estimates revealed the inverse associated with LC for the n-3 PUFA score. Ten lipids were identified as markers with an area under the curve (AUC) value of 0.947 (95%, CI: 0.879-0.989). In this study, we summarized the potential relationship between lipid molecules with different structural features and LC risk, identified a panel of LC biomarkers, and demonstrated that the n-3 PUFA of the acyl chain of lipids was a protective factor for LC.
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16
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Zhang J, He G, Jin X, Alenezi BT, Naeem AA, Abdulsamad SA, Ke Y. Molecular mechanisms on how FABP5 inhibitors promote apoptosis-induction sensitivity of prostate cancer cells. Cell Biol Int 2023; 47:929-942. [PMID: 36651331 DOI: 10.1002/cbin.11989] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2022] [Revised: 11/18/2022] [Accepted: 01/02/2023] [Indexed: 01/19/2023]
Abstract
Previous work showed that FABP5 inhibitors suppressed the malignant progression of prostate cancer cells, and this suppression might be achieved partially by promoting apoptosis. But the mechanisms involved were not known. Here, we investigated the effect of inhibitors on apoptosis and studied the relevant mechanisms. WtrFABP5 significantly reduced apoptotic cells in 22Rv1 and PC3 by 18% and 42%, respectively. In contrast, the chemical inhibitor SB-FI-26 produced significant increases in percentages of apoptotic cells in 22Rv1 and PC3 by 18.8% (±4.1) and 4.6% (±1.1), respectively. The bio- inhibitor dmrFABP5 also did so by 23.1% (±2.4) and 15.8% (±3.0), respectively, in these cell lines. Both FABP5 inhibitors significantly reduced the levels of the phosphorylated nuclear fatty acid receptor PPARγ, indicating that these inhibitors promoted apoptosis-induction sensitivity of the cancer cells by suppressing the biological activity of PPARγ. Thus, the phosphorylated PPARγ levels were reduced by FABP5 inhibitors, the levels of the phosphorylated AKT and activated nuclear factor kapper B (NFκB) were coordinately altered by additions of the inhibitors. These changes eventually led to the increased levels of cleaved caspase-9 and cleaved caspase-3; and thus, increase in the percentage of cells undergoing apoptosis. In untreated prostate cancer cells, increased FABP5 suppressed the apoptosis by increasing the biological activity of PPARγ, which, in turn, led to a reduced apoptosis by interfering with the AKT or NFκB signaling pathway. Our results suggested that the FABP5 inhibitors enhanced the apoptosis-induction of prostate cancer cells by reversing the biological effect of FABP5 and its related pathway.
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Affiliation(s)
- Jiacheng Zhang
- Department of Molecular and Clinical Cancer Medicine, Liverpool University, Liverpool, UK
| | - Gang He
- Sichuan Industrial Institute of Antibiotics, Chengdu University, Chengdu, Sichuan, China
| | - Xi Jin
- Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Bandar T Alenezi
- Department of Molecular and Clinical Cancer Medicine, Liverpool University, Liverpool, UK
| | - Abdulghani A Naeem
- Department of Molecular and Clinical Cancer Medicine, Liverpool University, Liverpool, UK
| | - Saud A Abdulsamad
- Department of Molecular and Clinical Cancer Medicine, Liverpool University, Liverpool, UK
| | - Youqiang Ke
- Department of Molecular and Clinical Cancer Medicine, Liverpool University, Liverpool, UK.,Sichuan Industrial Institute of Antibiotics, Chengdu University, Chengdu, Sichuan, China.,Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
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17
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Allenspach K, Borcherding DC, Iennarella-Servantez CA, Mosichuk AP, Atherly T, Sahoo DK, Kathrani A, Suchodolski JS, Bourgois-Mochel A, Serao MR, Serao NV, Willette A, Perez BA, Gabriel V, Mao S, Kilburn L, Dang V, Borts D, Almada LL, Fernandez-Zapico ME, Phillips GJ, Jergens AE, Mochel JP. Ketogenic diets in healthy dogs induce gut and serum metabolome changes suggestive of anti-tumourigenic effects: A model for human ketotherapy trials. Clin Transl Med 2022; 12:e1047. [PMID: 36149786 PMCID: PMC9506423 DOI: 10.1002/ctm2.1047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Revised: 08/15/2022] [Accepted: 08/23/2022] [Indexed: 12/02/2022] Open
Affiliation(s)
- Karin Allenspach
- Departments, of Veterinary Clinical Sciences, Iowa State University College of Veterinary Medicine, Ames, Iowa, USA
| | - Dana C Borcherding
- Department of Biomedical Sciences, Iowa State University College of Veterinary Medicine, Ames, Iowa, USA
| | - Chelsea A Iennarella-Servantez
- Department of Biomedical Sciences, Iowa State University College of Veterinary Medicine, Ames, Iowa, USA.,Royal Veterinary College, University of London, London, UK
| | - Allison P Mosichuk
- Departments, of Veterinary Clinical Sciences, Iowa State University College of Veterinary Medicine, Ames, Iowa, USA
| | - Todd Atherly
- Departments, of Veterinary Clinical Sciences, Iowa State University College of Veterinary Medicine, Ames, Iowa, USA
| | - Dipak Kumar Sahoo
- Department of Biomedical Sciences, Iowa State University College of Veterinary Medicine, Ames, Iowa, USA
| | - Aarti Kathrani
- Royal Veterinary College, University of London, London, UK
| | - Jan S Suchodolski
- Gastrointestinal Laboratory, Texas A&M University, College of Veterinary Medicine & Biomedical Sciences, College Station, Texas, USA
| | - Agnes Bourgois-Mochel
- Departments, of Veterinary Clinical Sciences, Iowa State University College of Veterinary Medicine, Ames, Iowa, USA
| | | | - Nick V Serao
- Department of Animal Science, Iowa State University, Ames, Iowa, USA
| | - Auriel Willette
- Food Science and Human Nutrition, Iowa State University, Ames, Iowa, USA
| | - Beatriz Agulla Perez
- Departments, of Veterinary Clinical Sciences, Iowa State University College of Veterinary Medicine, Ames, Iowa, USA
| | - Vojtech Gabriel
- Departments, of Veterinary Clinical Sciences, Iowa State University College of Veterinary Medicine, Ames, Iowa, USA
| | - Sichao Mao
- Departments, of Veterinary Clinical Sciences, Iowa State University College of Veterinary Medicine, Ames, Iowa, USA
| | - Logan Kilburn
- Department of Animal Science, Iowa State University, Ames, Iowa, USA
| | - Viet Dang
- Veterinary Diagnostics Laboratory, Iowa State University, Ames, Iowa, USA
| | - David Borts
- Veterinary Diagnostics Laboratory, Iowa State University, Ames, Iowa, USA
| | - Luciana L Almada
- Schulze Center for Novel Therapeutics, Division of Oncology Research, Mayo Clinic, Rochester, Minnesota, USA
| | - Martin E Fernandez-Zapico
- Schulze Center for Novel Therapeutics, Division of Oncology Research, Mayo Clinic, Rochester, Minnesota, USA
| | - Gregory J Phillips
- Department of Veterinary Microbiology and Preventive Medicine, Iowa State University, Ames, Iowa, USA
| | - Albert E Jergens
- Departments, of Veterinary Clinical Sciences, Iowa State University College of Veterinary Medicine, Ames, Iowa, USA
| | - Jonathan P Mochel
- Department of Biomedical Sciences, Iowa State University College of Veterinary Medicine, Ames, Iowa, USA
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18
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The Role of Transcription Factor PPAR-γ in the Pathogenesis of Psoriasis, Skin Cells, and Immune Cells. Int J Mol Sci 2022; 23:ijms23179708. [PMID: 36077103 PMCID: PMC9456565 DOI: 10.3390/ijms23179708] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2022] [Revised: 08/22/2022] [Accepted: 08/23/2022] [Indexed: 11/22/2022] Open
Abstract
The peroxisome proliferator-activated receptor PPAR-γ is one of three PPAR nuclear receptors that act as ligand-activated transcription factors. In immune cells, the skin, and other organs, PPAR-γ regulates lipid, glucose, and amino acid metabolism. The receptor translates nutritional, pharmacological, and metabolic stimuli into the changes in gene expression. The activation of PPAR-γ promotes cell differentiation, reduces the proliferation rate, and modulates the immune response. In the skin, PPARs also contribute to the functioning of the skin barrier. Since we know that the route from identification to the registration of drugs is long and expensive, PPAR-γ agonists already approved for other diseases may also represent a high interest for psoriasis. In this review, we discuss the role of PPAR-γ in the activation, differentiation, and proliferation of skin and immune cells affected by psoriasis and in contributing to the pathogenesis of the disease. We also evaluate whether the agonists of PPAR-γ may become one of the therapeutic options to suppress the inflammatory response in lesional psoriatic skin and decrease the influence of comorbidities associated with psoriasis.
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19
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Jiao J, Zheng Y, Zhang Q, Xia D, Zhang L, Ma N. Saliva microbiome changes in thyroid cancer and thyroid nodules patients. Front Cell Infect Microbiol 2022; 12:989188. [PMID: 36034695 PMCID: PMC9403763 DOI: 10.3389/fcimb.2022.989188] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2022] [Accepted: 07/21/2022] [Indexed: 11/13/2022] Open
Abstract
Objective Thyroid disease has been reported to associate with gut microbiota, but the effects of thyroid cancer and thyroid nodules on the oral microbiota are still largely unknown. This study aimed to identify the variation in salivary microbiota and their potential association with thyroid cancer and thyroid nodules. Methods We used 16S rRNA high-throughput sequencing to examine the salivary microbiota of thyroid cancer patients (n = 14), thyroid nodules patients (n = 9), and healthy controls (n = 15). Results The alpha-diversity indices Chao1 and ACE were found to be relatively higher in patients with thyroid cancer and thyroid nodules compared to healthy controls. The beta diversity in both the thyroid cancer and thyroid nodules groups was divergent from the healthy control group. The genera Alloprevotella, Anaeroglobus, Acinetobacter, unclassified Bacteroidales, and unclassified Cyanobacteriales were significantly enriched in the thyroid cancer group compared with the healthy control group. In contrast, the microbiome of the healthy controls was mainly composed of the genera Haemophilus, Lautropia, Allorhizobium Neorhizobium Pararhizobium Rhizobium, Escherichia Shigella, and unclassified Rhodobacteraceae. The thyroid nodules group was dominated by genre uncultured Candidatus Saccharibacteria bacterium, unclassified Clostridiales bacterium feline oral taxon 148, Treponema, unclassified Prevotellaceae, Mobiluncus, and Acholeplasma. In contrast, the genera unclassified Rhodobacteraceae and Aggregatibacter dominated the healthy control group. The study also found that clinical indicators were correlated with the saliva microbiome. Conclusion The salivary microbiota variation may be connected with thyroid cancer and thyroid nodules.
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Affiliation(s)
- Junjun Jiao
- Hospital of Stomatology, Jilin University, Changchun, China
| | - Youli Zheng
- The School and Hospital of Stomatology, Tianjin Medical University, Tianjin, China
| | - Qingyu Zhang
- Hospital of Stomatology, Jilin University, Changchun, China
| | - Degeng Xia
- Hospital of Stomatology, Jilin University, Changchun, China
| | - Li Zhang
- Hospital of Stomatology, Jilin University, Changchun, China
- *Correspondence: Ning Ma, ; Li Zhang,
| | - Ning Ma
- Hospital of Stomatology, Jilin University, Changchun, China
- *Correspondence: Ning Ma, ; Li Zhang,
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