Formononetin: A Review of Its Anticancer Potentials and Mechanisms
Cancer, a complex yet common disease, is caused by uncontrolled cell division and abnormal cell growth due to a variety of gene mutations. Seeking effective treatments for cancer is a major research focus, as the incidence of cancer is on the rise and drug resistance to existing anti-cancer drugs is...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-07-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2019.00820/full |
| _version_ | 1818358110251646976 |
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| author | Kai-Ching Tay Loh Teng-Hern Tan Loh Teng-Hern Tan Chim Kei Chan Sok Lai Hong Kok-Gan Chan Kok-Gan Chan Wei Hsum Yap Priyia Pusparajah Learn-Han Lee Learn-Han Lee Bey-Hing Goh Bey-Hing Goh |
| author_facet | Kai-Ching Tay Loh Teng-Hern Tan Loh Teng-Hern Tan Chim Kei Chan Sok Lai Hong Kok-Gan Chan Kok-Gan Chan Wei Hsum Yap Priyia Pusparajah Learn-Han Lee Learn-Han Lee Bey-Hing Goh Bey-Hing Goh |
| author_sort | Kai-Ching Tay |
| collection | DOAJ |
| description | Cancer, a complex yet common disease, is caused by uncontrolled cell division and abnormal cell growth due to a variety of gene mutations. Seeking effective treatments for cancer is a major research focus, as the incidence of cancer is on the rise and drug resistance to existing anti-cancer drugs is major concern. Natural products have the potential to yield unique molecules and combinations of substances that may be effective against cancer with relatively low toxicity/better side effect profile compared to standard anticancer therapy. Drug discovery work with natural products has demonstrated that natural compounds display a wide range of biological activities correlating to anticancer effects. In this review, we discuss formononetin (C16H12O4), which originates mainly from red clovers and the Chinese herb Astragalus membranaceus. The compound comes from a class of 7-hydroisoflavones with a substitution of methoxy group at position 4. Formononetin elicits antitumorigenic properties in vitro and in vivo by modulating numerous signaling pathways to induce cell apoptosis (by intrinsic pathway involving Bax, Bcl-2, and caspase-3 proteins) and cell cycle arrest (by regulating mediators like cyclin A, cyclin B1, and cyclin D1), suppress cell proliferation [by signal transducer and activator of transcription (STAT) activation, phosphatidylinositol 3-kinase/protein kinase-B (PI3K/AKT), and mitogen-activated protein kinase (MAPK) signaling pathway], and inhibit cell invasion [by regulating growth factors vascular endothelial growth factor (VEGF) and Fibroblast growth factor 2 (FGF2), and matrix metalloproteinase (MMP)-2 and MMP-9 proteins]. Co-treatment with other chemotherapy drugs such as bortezomib, LY2940002, U0126, sunitinib, epirubicin, doxorubicin, temozolomide, and metformin enhances the anticancer potential of both formononetin and the respective drugs through synergistic effect. Compiling the evidence thus far highlights the potential of formononetin to be a promising candidate for chemoprevention and chemotherapy. |
| first_indexed | 2024-12-13T20:23:47Z |
| format | Article |
| id | doaj.art-5137ca93efab49e5998c2bcdbfb33c37 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-13T20:23:47Z |
| publishDate | 2019-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-5137ca93efab49e5998c2bcdbfb33c372022-12-21T23:32:36ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122019-07-011010.3389/fphar.2019.00820457757Formononetin: A Review of Its Anticancer Potentials and MechanismsKai-Ching Tay0Loh Teng-Hern Tan1Loh Teng-Hern Tan2Chim Kei Chan3Sok Lai Hong4Kok-Gan Chan5Kok-Gan Chan6Wei Hsum Yap7Priyia Pusparajah8Learn-Han Lee9Learn-Han Lee10Bey-Hing Goh11Bey-Hing Goh12Biofunctional Molecule Exploratory (BMEX) Research Group, School of Pharmacy, Monash University Malaysia, Bandar Sunway, MalaysiaNovel Bacteria and Drug Discovery (NBDD) Research Group, Microbiome and Bioresource Research Strength Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway, MalaysiaInstitute of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, Chinade Duve Institute, Brussels, BelgiumCentre for Research Services, Institute of Research Management and Services, University of Malaya, Kuala Lumpur, MalaysiaDivision of Genetics and Molecular Biology, Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, MalaysiaInternational Genome Centre, Jiangsu University, Zhenjiang, ChinaSchool of Biosciences, Taylor’s University, Subang Jaya, MalaysiaMedical Health and Translational Research Group (MHTR), Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway, MalaysiaNovel Bacteria and Drug Discovery (NBDD) Research Group, Microbiome and Bioresource Research Strength Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway, Malaysia0Institute of Pharmaceutical Science, University of Veterinary and Animal Science, Lahore, PakistanBiofunctional Molecule Exploratory (BMEX) Research Group, School of Pharmacy, Monash University Malaysia, Bandar Sunway, Malaysia0Institute of Pharmaceutical Science, University of Veterinary and Animal Science, Lahore, PakistanCancer, a complex yet common disease, is caused by uncontrolled cell division and abnormal cell growth due to a variety of gene mutations. Seeking effective treatments for cancer is a major research focus, as the incidence of cancer is on the rise and drug resistance to existing anti-cancer drugs is major concern. Natural products have the potential to yield unique molecules and combinations of substances that may be effective against cancer with relatively low toxicity/better side effect profile compared to standard anticancer therapy. Drug discovery work with natural products has demonstrated that natural compounds display a wide range of biological activities correlating to anticancer effects. In this review, we discuss formononetin (C16H12O4), which originates mainly from red clovers and the Chinese herb Astragalus membranaceus. The compound comes from a class of 7-hydroisoflavones with a substitution of methoxy group at position 4. Formononetin elicits antitumorigenic properties in vitro and in vivo by modulating numerous signaling pathways to induce cell apoptosis (by intrinsic pathway involving Bax, Bcl-2, and caspase-3 proteins) and cell cycle arrest (by regulating mediators like cyclin A, cyclin B1, and cyclin D1), suppress cell proliferation [by signal transducer and activator of transcription (STAT) activation, phosphatidylinositol 3-kinase/protein kinase-B (PI3K/AKT), and mitogen-activated protein kinase (MAPK) signaling pathway], and inhibit cell invasion [by regulating growth factors vascular endothelial growth factor (VEGF) and Fibroblast growth factor 2 (FGF2), and matrix metalloproteinase (MMP)-2 and MMP-9 proteins]. Co-treatment with other chemotherapy drugs such as bortezomib, LY2940002, U0126, sunitinib, epirubicin, doxorubicin, temozolomide, and metformin enhances the anticancer potential of both formononetin and the respective drugs through synergistic effect. Compiling the evidence thus far highlights the potential of formononetin to be a promising candidate for chemoprevention and chemotherapy.https://www.frontiersin.org/article/10.3389/fphar.2019.00820/fullformononetinanticancerantitumorapoptosisanti-metastasis |
| spellingShingle | Kai-Ching Tay Loh Teng-Hern Tan Loh Teng-Hern Tan Chim Kei Chan Sok Lai Hong Kok-Gan Chan Kok-Gan Chan Wei Hsum Yap Priyia Pusparajah Learn-Han Lee Learn-Han Lee Bey-Hing Goh Bey-Hing Goh Formononetin: A Review of Its Anticancer Potentials and Mechanisms Frontiers in Pharmacology formononetin anticancer antitumor apoptosis anti-metastasis |
| title | Formononetin: A Review of Its Anticancer Potentials and Mechanisms |
| title_full | Formononetin: A Review of Its Anticancer Potentials and Mechanisms |
| title_fullStr | Formononetin: A Review of Its Anticancer Potentials and Mechanisms |
| title_full_unstemmed | Formononetin: A Review of Its Anticancer Potentials and Mechanisms |
| title_short | Formononetin: A Review of Its Anticancer Potentials and Mechanisms |
| title_sort | formononetin a review of its anticancer potentials and mechanisms |
| topic | formononetin anticancer antitumor apoptosis anti-metastasis |
| url | https://www.frontiersin.org/article/10.3389/fphar.2019.00820/full |
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