The cyclic peptide mallotumide A inhibits colon and breast cancer cell growth and motility by targeting cellular respiration and lipogenesis
Issued Date
2025-11-19
Resource Type
eISSN
20452322
Scopus ID
2-s2.0-105022224412
Pubmed ID
41258461
Journal Title
Scientific Reports
Volume
15
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
Scientific Reports Vol.15 No.1 (2025) , 40774
Suggested Citation
Laowittawat C., Sawektreeratana N., Katewongsa K., Payomhom P., Hongthong S., Reutrakul V., Kuhakarn C., Jitrapakdee S. The cyclic peptide mallotumide A inhibits colon and breast cancer cell growth and motility by targeting cellular respiration and lipogenesis. Scientific Reports Vol.15 No.1 (2025) , 40774. doi:10.1038/s41598-025-24547-x Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/113257
Title
The cyclic peptide mallotumide A inhibits colon and breast cancer cell growth and motility by targeting cellular respiration and lipogenesis
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Abstract
We have recently isolated, and determined the structure of a cycloheptapeptide, Mallotumide A from the Mallotus spodocarpus root extract. Here we reported the anti-cancer activity of Mallotumide A in highly invasive colon cancer, HCT116 and triple-negative breast cancer, MDA-MB-231 cell lines. Mallotumide A, at concentrations of 1 nM and 10 nM, completely inhibited the clonogenic growth, migration, and invasion of HCT116 and MDA-MB-231 cells, respectively. While the compound interfered with cell cycle progression without inducing apoptosis, exposure to 10 nM Mallotumide A for 48 h reduced the expression of two key lipogenic enzymes, ACC1 and FASN, by approximately 50% in both cell lines. The downregulation of ACC1 and FASN was accompanied by a 50% reduction in intracellular triglyceride levels while the cholesterol levels remained unaffected. Mallotumide A also moderately decreased AMP-activated protein kinase (AMPK) and ATP levels. Extracellular flux analysis revealed that acute exposure of both cancer cell lines to 1 nM and 10 nM Mallotumide A for 24 h markedly lowered the oxygen consumption rate. This was accompanied by reductions in basal and ATP-linked respiration, maximal respiration, and mitochondrial spare respiratory capacity. Mallotumide A also decreased the extracellular acidification rate, affecting both basal glycolysis and the glycolytic reserve. These findings suggest that the anti-cancer effects of Mallotumide A are associated with disruptions in cellular energy metabolism and the de novo lipogenesis pathway in cancer cells. This study underscores the potential of Mallotumide A as a novel anti-cancer agent.