Anti-metastatic function of triterpene phytochemicals from guggul by targeting tumor-intrinsic NF-kB activation in triple-negative breast cancer cells
Background: The endogenous activity of NF-κB is often elevated in various types of cancer cells, particularly breast cancer, and is strongly correlated with the induction of target genes that can inhibit apoptosis, interact with cell-cycle regulation, promote cell invasion and contribute to tumorige...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-11-01
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| Series: | Phytomedicine Plus |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667031322001269 |
| _version_ | 1811311136067289088 |
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| author | Amira A. Abdellatef Meselhy R. Meselhy Hesham I. El-Askary Sahar El-mekkawy Yoshihiro Hayakawa |
| author_facet | Amira A. Abdellatef Meselhy R. Meselhy Hesham I. El-Askary Sahar El-mekkawy Yoshihiro Hayakawa |
| author_sort | Amira A. Abdellatef |
| collection | DOAJ |
| description | Background: The endogenous activity of NF-κB is often elevated in various types of cancer cells, particularly breast cancer, and is strongly correlated with the induction of target genes that can inhibit apoptosis, interact with cell-cycle regulation, promote cell invasion and contribute to tumorigenesis, inflammation, and metastatic growth as well as drug resistance. Thus, the downregulation of NF-κB is regarded as a promising therapeutic target to inhibit breast cancer growth and metastasis. Purpose: Since no NF-κB inhibitor has yet been approved by the FDA, we aim to identify small molecules from natural resources that could potentially inhibit NF-κB and suppress breast cancer metastasis. Study design: In the current study, nineteen extracts from different valuable medicinal plants were screened for their prospective biological activity against NF-κB transcriptional activation in 4T1 breast cancer cells, followed by isolation and purification analysis of the major active compounds from guggul extract, as it exhibited the most inhibitory efficacy of NF-κB activation. Results: A bioassay-guided isolation of active constituents from the promising candidate, guggul methanol extract (GU-M), using NF-κB reporter gene assay was performed to identify potential anti-metastatic agents for triple-negative breast cancer cells (TNBC) and resulted in the isolation of four known major compounds namely; guggulsterone M (1), guggulsterol Ι (2), myyrhanol A (3), and myyrhanone A (4). Conclusion: Among the isolated compounds, myrrhanol A and myrrhanone A at the concentration of 10 μM markedly inhibited the intrinsic NF-κB pathway and potently suppressed the proliferative and metastatic abilities of murine and human breast cancer cells; 4T1, MDA-MB-231, and MDA-MB-453. |
| first_indexed | 2024-04-13T10:12:26Z |
| format | Article |
| id | doaj.art-e1f2ff8cff31475eb017a6707befe064 |
| institution | Directory Open Access Journal |
| issn | 2667-0313 |
| language | English |
| last_indexed | 2024-04-13T10:12:26Z |
| publishDate | 2022-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Phytomedicine Plus |
| spelling | doaj.art-e1f2ff8cff31475eb017a6707befe0642022-12-22T02:50:53ZengElsevierPhytomedicine Plus2667-03132022-11-0124100345Anti-metastatic function of triterpene phytochemicals from guggul by targeting tumor-intrinsic NF-kB activation in triple-negative breast cancer cellsAmira A. Abdellatef0Meselhy R. Meselhy1Hesham I. El-Askary2Sahar El-mekkawy3Yoshihiro Hayakawa4Section of Host Defences, Institute of Natural Medicine, University of Toyama, Toyama, JapanDepartment of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo, EgyptDepartment of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo, EgyptDepartment of Natural Compounds, National Research Centre, EgyptSection of Host Defences, Institute of Natural Medicine, University of Toyama, Toyama, Japan; Corresponding author at: Institute of Natural Medicine, University of Toyama, Sugitani 2630, Toyama, 930-0194, Japan.Background: The endogenous activity of NF-κB is often elevated in various types of cancer cells, particularly breast cancer, and is strongly correlated with the induction of target genes that can inhibit apoptosis, interact with cell-cycle regulation, promote cell invasion and contribute to tumorigenesis, inflammation, and metastatic growth as well as drug resistance. Thus, the downregulation of NF-κB is regarded as a promising therapeutic target to inhibit breast cancer growth and metastasis. Purpose: Since no NF-κB inhibitor has yet been approved by the FDA, we aim to identify small molecules from natural resources that could potentially inhibit NF-κB and suppress breast cancer metastasis. Study design: In the current study, nineteen extracts from different valuable medicinal plants were screened for their prospective biological activity against NF-κB transcriptional activation in 4T1 breast cancer cells, followed by isolation and purification analysis of the major active compounds from guggul extract, as it exhibited the most inhibitory efficacy of NF-κB activation. Results: A bioassay-guided isolation of active constituents from the promising candidate, guggul methanol extract (GU-M), using NF-κB reporter gene assay was performed to identify potential anti-metastatic agents for triple-negative breast cancer cells (TNBC) and resulted in the isolation of four known major compounds namely; guggulsterone M (1), guggulsterol Ι (2), myyrhanol A (3), and myyrhanone A (4). Conclusion: Among the isolated compounds, myrrhanol A and myrrhanone A at the concentration of 10 μM markedly inhibited the intrinsic NF-κB pathway and potently suppressed the proliferative and metastatic abilities of murine and human breast cancer cells; 4T1, MDA-MB-231, and MDA-MB-453.http://www.sciencedirect.com/science/article/pii/S2667031322001269Commiphora wightiiGuggulTriterpenesNF-κBBreast cancerMetastasis |
| spellingShingle | Amira A. Abdellatef Meselhy R. Meselhy Hesham I. El-Askary Sahar El-mekkawy Yoshihiro Hayakawa Anti-metastatic function of triterpene phytochemicals from guggul by targeting tumor-intrinsic NF-kB activation in triple-negative breast cancer cells Phytomedicine Plus Commiphora wightii Guggul Triterpenes NF-κB Breast cancer Metastasis |
| title | Anti-metastatic function of triterpene phytochemicals from guggul by targeting tumor-intrinsic NF-kB activation in triple-negative breast cancer cells |
| title_full | Anti-metastatic function of triterpene phytochemicals from guggul by targeting tumor-intrinsic NF-kB activation in triple-negative breast cancer cells |
| title_fullStr | Anti-metastatic function of triterpene phytochemicals from guggul by targeting tumor-intrinsic NF-kB activation in triple-negative breast cancer cells |
| title_full_unstemmed | Anti-metastatic function of triterpene phytochemicals from guggul by targeting tumor-intrinsic NF-kB activation in triple-negative breast cancer cells |
| title_short | Anti-metastatic function of triterpene phytochemicals from guggul by targeting tumor-intrinsic NF-kB activation in triple-negative breast cancer cells |
| title_sort | anti metastatic function of triterpene phytochemicals from guggul by targeting tumor intrinsic nf kb activation in triple negative breast cancer cells |
| topic | Commiphora wightii Guggul Triterpenes NF-κB Breast cancer Metastasis |
| url | http://www.sciencedirect.com/science/article/pii/S2667031322001269 |
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