Isolation, Characterization and Anticancer Evaluation of Alkaloids from Eumachia montana (Rubiaceae)Tools Shuai, Yuye (2025) Isolation, Characterization and Anticancer Evaluation of Alkaloids from Eumachia montana (Rubiaceae). PhD thesis, University of Nottingham.
AbstractThe dimeric (-)-calycanthine (1), the hexameric (+)-oleoidine (2), the heptameric (+)-caledonine (3), the octameric (+)-eumatanine (4) and a tricyclic pyrroloquinoline alkaloid, eumatricine (5) are alkaloids isolated from the leaves of Eumachia montana; compounds 4 and 5 are previously uncharacterized alkaloids. Preliminary anticancer assays, including MTT, cell count and clonogenic assays, revealed potent inhibition of cell growth and colony formation by compounds 2-4 against seven carcinoma cell lines (including breast, colorectal, lung and glioblastoma multiforme cell lines). The GI50 values of compounds 2-4 ranged from 0.1 to 2.7µM, and potent cytotoxic activity against HCT-116 and MCF-7 was observed (3 > 4 > 2). Cell cycle analysis and apoptosis assays revealed that compound 3 and 4 evokes profound apoptosis without cell cycle phase-specific arrest (under most circumstance except in MCF-7 cells when against 4 at 1 × GI50 for 24h). Additionally, compound 4 also activated caspase, further corroborating the conclusion of apoptosis-induction. Detection of ROS induced by 4 infers a role for oxidative stress in anticancer activity, while γH2AX detection indicates the presence of DNA double strand breaks. Visualization of 4-treated cells by fluorescence microscopy implies multiple cell death pathways are simultaneously triggered (e.g., apoptosis, autophagy, necrosis and paraptosis). Furthermore, metabolomic analysis of 3 and 4 highlights their disruption of membrane integrity through the upregulation of glycerophosphoethanolamine (GPE), glycerophosphocholine (GPC), and acetylcholine (ACh), reinforcing their role in apoptosis induction. These findings provide valuable insights into the mechanism of action of these compounds and their potential as anticancer agents.
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