title: Antiproliferative and apoptotic effects of compounds from the flower of Mammea siamensis (Miq.) T. Anders. on human cancer cell lines.
abstract: On the search for anti-cancer compounds from Thai traditional herb medicines, a bioassay-guided fractionation and chemical investigation of the methanol extract of Mammea siamensis flower resulted in the isolation and identification of eight compounds (1-8) including a novel geranylated coumarin, namely mammeanoyl (2), and seven known compounds (1 and 3-8). The structure of new compound 2 was elucidated based on the extensive spectroscopic and chemical methods. Among the isolated compounds, three structurally related coumarins 3, 4, and 5 showed significant antiproliferative activities against human leukemia and stomach cancer cell lines. However, these compounds did not affect the cell viabilities of colon cancer, hepatoma, and normal skin fibroblast cell lines. Further analysis demonstrated that the morphological features of apoptosis including DNA fragmentation and chromatin condensation were observed in human leukemia HL-60 cells treated with compounds 3, 4, and 5. In addition, compound 3 led to caspase-3 activation and cleavage of poly (ADP-ribose) polymerase (PARP), and compound 3-induced DNA fragmentation was inhibited by caspase-specific inhibitors. These results suggest that compound 3, 4, and 5 exert antiproliferative actions through apoptotic cell death in leukemia cells and these compounds may have the potential to be developed into new anti-cancer drug candidates.
authors.affiliation: Department of Pharmacognosy, Faculty of Pharmaceutical Sciences, Nagasaki International University, 2825-7 Huis Ten Bosch, Sasebo, Nagasaki 859-3298, Japan.
authors.forename: Nguyen Huu
authors.initials: NH
authors.lastname: Tung
authors.forename: Takuhiro
authors.initials: T
authors.lastname: Uto
authors.forename: Ayana
authors.initials: A
authors.lastname: Sakamoto
authors.forename: Yuka
authors.initials: Y
authors.lastname: Hayashida
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Hidaka
authors.forename: Osamu
authors.initials: O
authors.lastname: Morinaga
authors.forename: Sorasak
authors.initials: S
authors.lastname: Lhieochaiphant
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Shoyama
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D003374:Coumarins / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D053938:DNA Fragmentation; D004354:Drug Screening Assays, Antitumor; D035264:Flowers / Q000737:chemistry; D018922:HL-60 Cells; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D031252:Mammea / Q000737:chemistry*; D008968:Molecular Conformation; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D003374:Coumarins; D004247:DNA; C030123:coumarin; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3