{"doi":"10.1186/s12964-024-01951-w","title":"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 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.","journal":"Cell Communication and Signaling","year":2024,"id":439437,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9667,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1250770,"name":"Ellen T. Tran","orcid":null,"position":1,"is_corresponding":false},{"id":1250771,"name":"Ruchi A. Patel","orcid":null,"position":2,"is_corresponding":false},{"id":1250772,"name":"Matthew Luetzen","orcid":null,"position":3,"is_corresponding":false},{"id":357055,"name":"Kevin Cho","orcid":"0000-0002-3041-3506","position":4,"is_corresponding":false},{"id":388961,"name":"Leah P. Shriver","orcid":"0000-0001-5673-0940","position":5,"is_corresponding":false},{"id":186110,"name":"Gary J. Patti","orcid":"0000-0002-3748-6193","position":6,"is_corresponding":false},{"id":465044,"name":"Mark A. Varvares","orcid":"0000-0002-6570-5672","position":7,"is_corresponding":false},{"id":380621,"name":"David A. Ford","orcid":"0000-0002-0029-1560","position":8,"is_corresponding":false},{"id":258402,"name":"Kyle S. McCommis","orcid":"0000-0003-2381-1589","position":9,"is_corresponding":false},{"id":284928,"name":"Ratna B. Ray","orcid":"0000-0003-4477-6292","position":10,"is_corresponding":false},{"id":1250181,"name":"Debojyoty Bandyopadhyay","orcid":"0000-0002-2726-1791","position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":null,"created_at":"2026-07-19T02:00:47.992543Z","pmid":"39696286","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}