title: Mangiferin induces apoptosis by suppressing Bcl-xL and XIAP expressions and nuclear entry of NF-κB in HL-60 cells.
abstract: Mangiferin, 1,3,6,7-tetrahydroxyxanthone-C2-β-D: -glucoside (C-glucosylxanthone), is a xanthone derivative that is widely distributed in higher plants. Recently, mangiferin was found to exhibit potential antitumor effects. However, the molecular mechanisms of this effect have not been elucidated. In the present study, we attempt to clarify the mechanism of mangiferin-induced apoptosis in the human acute myeloid leukemia cell line HL-60; mangiferin was found to induce apoptosis. We also observed a concurrent increase in caspase-3 activity and DNA fragmentation. Furthermore, on examining the survival signals expressed during apoptotic induction, we observed that mangiferin caused a remarkable decrease in the nuclear entry of NF-κB p65. However, there were no changes in the expression of other survival signals, such as extracellular signal-regulated kinase 1/2, protein kinase B, and p38 mitogenactivated protein kinase. In addition, mangiferin suppressed the expressions of Bcl-xL and XIAP; however, we did not note any changes in the levels of Bcl-2, Bax, and Bim. These results indicate that mangiferin induces apoptosis by suppressing NF-κB activation and expressions of Bcl-xL and XAIP. These findings suggest that mangiferin may be useful as an anticancer agent and can be used in combination therapy with other anticancer drugs for the treatment of acute myeloid leukemia.
authors.affiliation: Division of Pharmacotherapy, Kinki University School of Pharmacy, Kowakae, Higashi-Osaka, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Shoji
authors.forename: Masanobu
authors.initials: M
authors.lastname: Tsubaki
authors.forename: Yuzuru
authors.initials: Y
authors.lastname: Yamazoe
authors.forename: Takao
authors.initials: T
authors.lastname: Satou
authors.forename: Tatsuki
authors.initials: T
authors.lastname: Itoh
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kidera
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Tanimori
authors.forename: Masashi
authors.initials: M
authors.lastname: Yanae
authors.forename: Hideaki
authors.initials: H
authors.lastname: Matsuda
authors.forename: Atsushi
authors.initials: A
authors.lastname: Taga
authors.forename: Haruyuki
authors.initials: H
authors.lastname: Nakamura
authors.forename: Shozo
authors.initials: S
authors.lastname: Nishida
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects* / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D018922:HL-60 Cells; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D021381:Protein Transport; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D044004:Xanthones / Q000494:pharmacology*; D051020:bcl-X Protein / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C494811:BCL2L1 protein, human; D016328:NF-kappa B; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; D044004:Xanthones; D051020:bcl-X Protein; C013592:mangiferin; D053148:Caspase 3