Momordicine-I suppresses head and neck cancer growth by modulating key metabolic pathways
Abstract One of the hallmarks of cancer is metabolic reprogramming which controls cellular homeostasis and therapy resistance. Here, we investigated the effect of momordicine-I (M-I), a key bioactive compound from Momordica charantia (bitter melon), on metabolic pathways in human head and neck cance...
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| Format: | Article |
| Language: | English |
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BMC
2024-12-01
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| Series: | Cell Communication and Signaling |
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| Online Access: | https://doi.org/10.1186/s12964-024-01951-w |
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| author | Debojyoty Bandyopadhyay Ellen T. Tran Ruchi A. Patel Matthew A. Luetzen Kevin Cho Leah P. Shriver Gary J. Patti Mark A. Varvares David A. Ford Kyle S. McCommis Ratna B. Ray |
| author_facet | Debojyoty Bandyopadhyay Ellen T. Tran Ruchi A. Patel Matthew A. Luetzen Kevin Cho Leah P. Shriver Gary J. Patti Mark A. Varvares David A. Ford Kyle S. McCommis Ratna B. Ray |
| author_sort | Debojyoty Bandyopadhyay |
| collection | DOAJ |
| description | Abstract One of the hallmarks of cancer is metabolic reprogramming which controls cellular homeostasis and therapy resistance. Here, we investigated the effect of momordicine-I (M-I), a key bioactive compound from Momordica charantia (bitter melon), on metabolic pathways in human head and neck cancer (HNC) cells and a mouse HNC tumorigenicity model. We found that M-I treatment on HNC cells significantly reduced the expression of key glycolytic molecules, SLC2A1 (GLUT-1), HK1, PFKP, PDK3, PKM, and LDHA at the mRNA and protein levels. We further observed reduced lactate accumulation, suggesting glycolysis was perturbed in M-I treated HNC cells. Metabolomic analyses confirmed a marked reduction in glycolytic and TCA cycle metabolites in M-I-treated cells. M-I treatment significantly downregulated mRNA and protein expression of essential enzymes involved in de novo lipogenesis, including ACLY, ACC1, FASN, SREBP1, and SCD1. Using shotgun lipidomics, we found a significant increase in lysophosphatidylcholine and phosphatidylcholine loss in M-I treated cells. Subsequently, we observed dysregulation of mitochondrial membrane potential and significant reduction of mitochondrial oxygen consumption after M-I treatment. We further observed M-I treatment induced autophagy, activated AMPK and inhibited mTOR and Akt signaling pathways and leading to apoptosis. However, blocking autophagy did not rescue the M-I-mediated alterations in lipogenesis, suggesting an independent mechanism of action. M-I treated mouse HNC MOC2 cell tumors displayed reduced Hk1, Pdk3, Fasn, and Acly expression. In conclusion, our study revealed that M-I inhibits glycolysis, lipid metabolism, induces autophagy in HNC cells and reduces tumor volume in mice. Therefore, M-I-mediated metabolic reprogramming of HNC has the potential for important therapeutic implications. Graphical Abstract |
| format | Article |
| id | doaj-art-53e079cdddbe4629a41123f4bb82d4fa |
| institution | DOAJ |
| issn | 1478-811X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | BMC |
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| series | Cell Communication and Signaling |
| spelling | doaj-art-53e079cdddbe4629a41123f4bb82d4fa2025-08-20T02:39:41ZengBMCCell Communication and Signaling1478-811X2024-12-0122111310.1186/s12964-024-01951-wMomordicine-I suppresses head and neck cancer growth by modulating key metabolic pathwaysDebojyoty Bandyopadhyay0Ellen T. Tran1Ruchi A. Patel2Matthew A. Luetzen3Kevin Cho4Leah P. Shriver5Gary J. Patti6Mark A. Varvares7David A. Ford8Kyle S. McCommis9Ratna B. Ray10Department of Pathology, Saint Louis UniversityDepartment of Pathology, Saint Louis UniversityDepartment of Pathology, Saint Louis UniversityBiochemistry & Molecular Biology, Saint Louis UniversityDepartment of Chemistry and Medicine, Washington UniversityDepartment of Chemistry and Medicine, Washington UniversityDepartment of Chemistry and Medicine, Washington UniversityDepartment of Otolaryngology, Head and Neck Surgery, Harvard Medical School, Massachusetts Eye and EarBiochemistry & Molecular Biology, Saint Louis UniversityBiochemistry & Molecular Biology, Saint Louis UniversityDepartment of Pathology, Saint Louis UniversityAbstract One of the hallmarks of cancer is metabolic reprogramming which controls cellular homeostasis and therapy resistance. Here, we investigated the effect of momordicine-I (M-I), a key bioactive compound from Momordica charantia (bitter melon), on metabolic pathways in human head and neck cancer (HNC) cells and a mouse HNC tumorigenicity model. We found that M-I treatment on HNC cells significantly reduced the expression of key glycolytic molecules, SLC2A1 (GLUT-1), HK1, PFKP, PDK3, PKM, and LDHA at the mRNA and protein levels. We further observed reduced lactate accumulation, suggesting glycolysis was perturbed in M-I treated HNC cells. Metabolomic analyses confirmed a marked reduction in glycolytic and TCA cycle metabolites in M-I-treated cells. M-I treatment significantly downregulated mRNA and protein expression of essential enzymes involved in de novo lipogenesis, including ACLY, ACC1, FASN, SREBP1, and SCD1. Using shotgun lipidomics, we found a significant increase in lysophosphatidylcholine and phosphatidylcholine loss in M-I treated cells. Subsequently, we observed dysregulation of mitochondrial membrane potential and significant reduction of mitochondrial oxygen consumption after M-I treatment. We further observed M-I treatment induced autophagy, activated AMPK and inhibited mTOR and Akt signaling pathways and leading to apoptosis. However, blocking autophagy did not rescue the M-I-mediated alterations in lipogenesis, suggesting an independent mechanism of action. M-I treated mouse HNC MOC2 cell tumors displayed reduced Hk1, Pdk3, Fasn, and Acly expression. In conclusion, our study revealed that M-I inhibits glycolysis, lipid metabolism, induces autophagy in HNC cells and reduces tumor volume in mice. Therefore, M-I-mediated metabolic reprogramming of HNC has the potential for important therapeutic implications. Graphical Abstracthttps://doi.org/10.1186/s12964-024-01951-wMomordicine-IHead and neck cancerGlycolysisLipid metabolismMetabolitesAutophagy |
| spellingShingle | Debojyoty Bandyopadhyay Ellen T. Tran Ruchi A. Patel Matthew A. Luetzen Kevin Cho Leah P. Shriver Gary J. Patti Mark A. Varvares David A. Ford Kyle S. McCommis Ratna B. Ray Momordicine-I suppresses head and neck cancer growth by modulating key metabolic pathways Cell Communication and Signaling Momordicine-I Head and neck cancer Glycolysis Lipid metabolism Metabolites Autophagy |
| title | Momordicine-I suppresses head and neck cancer growth by modulating key metabolic pathways |
| title_full | Momordicine-I suppresses head and neck cancer growth by modulating key metabolic pathways |
| title_fullStr | Momordicine-I suppresses head and neck cancer growth by modulating key metabolic pathways |
| title_full_unstemmed | Momordicine-I suppresses head and neck cancer growth by modulating key metabolic pathways |
| title_short | Momordicine-I suppresses head and neck cancer growth by modulating key metabolic pathways |
| title_sort | momordicine i suppresses head and neck cancer growth by modulating key metabolic pathways |
| topic | Momordicine-I Head and neck cancer Glycolysis Lipid metabolism Metabolites Autophagy |
| url | https://doi.org/10.1186/s12964-024-01951-w |
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