Isolation, Characterization, and Anticancer Evaluation of Alkaloids from (Rubiaceae).

The dimeric (-)-calycanthine (), the hexameric (+)-oleoidine (), the heptameric (+)-caledonine (), the octameric (+)-eumatanine (), and a tricyclic pyrroloquinoline alkaloid, eumatricine (), are alkaloids isolated from the leaves of ; compounds and are novel, previously uncharacterized alkaloids. Preliminary anticancer assays, including MTT, cell count, and clonogenic assays, revealed potent inhibition of cell growth and colony formation by compounds against seven carcinoma cell lines (including breast, colorectal, lung, and glioblastoma multiforme cell lines). The GI values of compounds ranged from 0.1 to 2.7 μM, and potent cytotoxic activity against HCT-116 and MCF-7 was observed ( > > ). Cell cycle analysis and apoptosis assays revealed that compound evokes profound apoptosis without cell cycle phase-specific arrest, accompanied by caspase activation, corroborating apoptosis-induction. Detection of ROS induced by infers a role for oxidative stress in anticancer activity. γH2AX detection indicates the presence of DNA double-strand breaks in cells treated with compound . Visualization of -treated cells by fluorescence microscopy implies multiple cell death pathways are simultaneously triggered (e.g., apoptosis, autophagy, necrosis, and paraptosis).