Natural Products and Small Molecules Targeting Cellular Ceramide Metabolism to Enhance Apoptosis in Cancer Cells
Molecular targeting strategies have been used for years in order to control cancer progression and are often based on targeting various enzymes involved in metabolic pathways. Keeping this in mind, it is essential to determine the role of each enzyme in a particular metabolic pathway. In this review...
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| Veröffentlicht in: | Cancers 2023-09, Vol.15 (18), p.4645 |
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| creator | Afrin, Farjana Mateen, Sameena Oman, Jordan Lai, James C K Barrott, Jared J Pashikanti, Srinath |
| description | Molecular targeting strategies have been used for years in order to control cancer progression and are often based on targeting various enzymes involved in metabolic pathways. Keeping this in mind, it is essential to determine the role of each enzyme in a particular metabolic pathway. In this review, we provide in-depth information on various enzymes such as ceramidase, sphingosine kinase, sphingomyelin synthase, dihydroceramide desaturase, and ceramide synthase which are associated with various types of cancers. We also discuss the physicochemical properties of well-studied inhibitors with natural product origins and their related structures in terms of these enzymes. Targeting ceramide metabolism exhibited promising mono- and combination therapies at preclinical stages in preventing cancer progression and cemented the significance of sphingolipid metabolism in cancer treatments. Targeting ceramide-metabolizing enzymes will help medicinal chemists design potent and selective small molecules for treating cancer progression at various levels. |
| doi_str_mv | 10.3390/cancers15184645 |
| format | Article |
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Keeping this in mind, it is essential to determine the role of each enzyme in a particular metabolic pathway. In this review, we provide in-depth information on various enzymes such as ceramidase, sphingosine kinase, sphingomyelin synthase, dihydroceramide desaturase, and ceramide synthase which are associated with various types of cancers. We also discuss the physicochemical properties of well-studied inhibitors with natural product origins and their related structures in terms of these enzymes. Targeting ceramide metabolism exhibited promising mono- and combination therapies at preclinical stages in preventing cancer progression and cemented the significance of sphingolipid metabolism in cancer treatments. Targeting ceramide-metabolizing enzymes will help medicinal chemists design potent and selective small molecules for treating cancer progression at various levels.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers15184645</identifier><identifier>PMID: 37760612</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Apoptosis ; Biological products ; Biosynthesis ; Cancer ; Cancer therapies ; Catalysis ; Cell cycle ; Cell differentiation ; Cell proliferation ; Ceramidase ; Ceramide ; Chemotherapy ; Cytotoxicity ; Desaturase ; Enzymes ; Genes ; Health aspects ; Kinases ; Lipid metabolism ; Lipids ; Metabolic pathways ; Metabolism ; Metabolites ; Natural products ; Oncology, Experimental ; Pancreatic cancer ; Pharmaceutical sciences ; Physicochemical properties ; Physiological aspects ; Physiology ; Prevention ; Proteins ; Radiation ; Review ; Sphingomyelin ; Sphingosine ; Sphingosine kinase ; Vemurafenib</subject><ispartof>Cancers, 2023-09, Vol.15 (18), p.4645</ispartof><rights>COPYRIGHT 2023 MDPI AG</rights><rights>2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). 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Targeting ceramide-metabolizing enzymes will help medicinal chemists design potent and selective small molecules for treating cancer progression at various levels.</description><subject>Apoptosis</subject><subject>Biological products</subject><subject>Biosynthesis</subject><subject>Cancer</subject><subject>Cancer therapies</subject><subject>Catalysis</subject><subject>Cell cycle</subject><subject>Cell differentiation</subject><subject>Cell proliferation</subject><subject>Ceramidase</subject><subject>Ceramide</subject><subject>Chemotherapy</subject><subject>Cytotoxicity</subject><subject>Desaturase</subject><subject>Enzymes</subject><subject>Genes</subject><subject>Health aspects</subject><subject>Kinases</subject><subject>Lipid metabolism</subject><subject>Lipids</subject><subject>Metabolic pathways</subject><subject>Metabolism</subject><subject>Metabolites</subject><subject>Natural products</subject><subject>Oncology, Experimental</subject><subject>Pancreatic cancer</subject><subject>Pharmaceutical sciences</subject><subject>Physicochemical properties</subject><subject>Physiological aspects</subject><subject>Physiology</subject><subject>Prevention</subject><subject>Proteins</subject><subject>Radiation</subject><subject>Review</subject><subject>Sphingomyelin</subject><subject>Sphingosine</subject><subject>Sphingosine kinase</subject><subject>Vemurafenib</subject><issn>2072-6694</issn><issn>2072-6694</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNptkk1PHSEUhidNGzXWtbuGpJturvI1wKyamxv7kWg1qV0ThjlcMQxMYaZJ_325aq2awoITeM7LeeE0zTHBJ4x1-NSaaCEX0hLFBW9fNQcUS7oSouOvn8T7zVEpt7gOxogUcq_ZZ1IKLAg9aKZvZl6yCegqp2Gxc0EmDuj7aEJAFymAXQIUdG3yFmYft2gDISzB5BpkM_oB0AXMpk_BlxHNCZ3Fm11VaD2laU7FF-Qj2twVepdb3jZvnAkFjh7Ww-bHp7PrzZfV-eXnr5v1-cpy1c0rx7DjrcEDsB4G6cA5DFZJUIJj2vdctEoMXDJoW0NULwmHoe2dUo4y6A07bD7e605LP8JgIc7Vpp6yH03-rZPx-vlJ9Dd6m35pglsqMe2qwocHhZx-LlBmPfpiqwcTIS1FUyUx4V2lK_r-BXqblhyrv0qJjuEW8-4ftTUBtI8u1YvtTlSvZf0pqjBRlTr5D1XnAKO3KYLzdf9Zwul9gs2plAzu0STBetco-kWj1Ix3T9_mkf_bFuwPo_S68g</recordid><startdate>20230920</startdate><enddate>20230920</enddate><creator>Afrin, Farjana</creator><creator>Mateen, Sameena</creator><creator>Oman, Jordan</creator><creator>Lai, James C K</creator><creator>Barrott, Jared J</creator><creator>Pashikanti, Srinath</creator><general>MDPI AG</general><general>MDPI</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7TO</scope><scope>7XB</scope><scope>8FE</scope><scope>8FH</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20230920</creationdate><title>Natural Products and Small Molecules Targeting Cellular Ceramide Metabolism to Enhance Apoptosis in Cancer Cells</title><author>Afrin, Farjana ; 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| subjects | Apoptosis Biological products Biosynthesis Cancer Cancer therapies Catalysis Cell cycle Cell differentiation Cell proliferation Ceramidase Ceramide Chemotherapy Cytotoxicity Desaturase Enzymes Genes Health aspects Kinases Lipid metabolism Lipids Metabolic pathways Metabolism Metabolites Natural products Oncology, Experimental Pancreatic cancer Pharmaceutical sciences Physicochemical properties Physiological aspects Physiology Prevention Proteins Radiation Review Sphingomyelin Sphingosine Sphingosine kinase Vemurafenib |
| title | Natural Products and Small Molecules Targeting Cellular Ceramide Metabolism to Enhance Apoptosis in Cancer Cells |
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