Bcl-2 and Caspase-3 Are Major Regulators in Agaricus blazei-Induced Human Leukemic U937 Cell Apoptosis through Dephoshorylation of Akt(Pharmacology)

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概要

• 論文の詳細を見る

• Agaricus blazei is a medicinal mushroom that possesses antimetastatic, antitumor, antimutagenic, and immunostimulating effects. However, the molecular mechanisms involved in A. blazei-mediated apoptosis remain unclear. In the present study, to elucidate the role of the Bcl-2 in A. blazei-mediated apoptosis, U937 cells were transfected with either empty vector (U937/vec) or vector containing cDNA encoding full-length Bcl-2 (U937/Bcl-2). As compared with U937/vec, U937/Bcl-2 cells exhibited a 4-fold greater expression of Bcl-2. Treatment of U937/vec with 1.0-4.0mg/ml of A. blazei extract (ABE) for 24 h resulted in a significant induction of morphologic features indicative of apoptosis. In contrast, U937/Bcl-2 exposed to the same ABE treatment only exhibited a slight induction of apoptotic features. ABE-induced apoptosis was accompanied by downregulation of antiapoptotic proteins such as X-linked inhibitor of apoptosis protein (XIAP), inhibitor of apoptosis protein (cIAP)-2 and Bcl-2, activation of caspase-3, and cleavage of poly(ADP-ribose)polymerase (PARP). Ectopic expression of Bcl-2 was associated with significantly induced expression of antiapoptotic proteins, such as cIAP-2 and Bcl-2, but not XIAP. Ectopic expression of Bcl-2 also reduced caspase-3 activation and PARP cleavage in ABE treated U937 cells. Furthermore, treatment with the caspase-3 inhibitor z-DEVD-fmk was sufficient to restore cell viability following ABE treatment. This increase in viability was ascribed to downregulation of caspase-3 and blockage of PARP and PLC-γ cleavage. ABE also triggered the downregulation of Akt, and combined treatment with LY294002 (an inhibitor of Akt) significantly decreased cell viability. The results indicated that major regulators of ABE-induced apoptosis in human leukemic U937 cells are Bcl-2 and caspase-3, which are associated with dephosphorylation of the Akt signal pathway.

• 社団法人日本薬学会の論文
• 2007-08-01

著者

• MOON Dong-Oh

  Faculty of Applied Marine Science, Cheju National University

• JIN Cheng-Yun

  Department of Microbiology, College of Natural Sciences, Pusan National University

• LEE Jae-Dong

  Department of Microbiology, College of Natural Sciences, Pusan National University

• CHOI Yung

  Department of Oriental Medicine, Dongeui University College of Oriental Medicine

• KIM Gi-Young

  Faculty of Applied Marine Science, Cheju National University

• Choi Yung

  韓国

• Moon Dong-oh

  韓国

• Lee J‐d

  Department Of Microbiology College Of Natural Sciences Pusan National University

• Moon Dong-oh

  Faculty Of Applied Marine Science Cheju National University

• Kim Gi-young

  韓国

• Kim Gi-young

  Faculty Of Applied Marine Science Cheju National University

• Lee Jun

  Department Of Pharmacy College Of Pharmacy Pusan National University

• Lee Jun-sik

  Dep. Of Microbiology And Immunology Pusan National Univ. Coll. Of Medicine

• Lee Jun-sik

  Department Of Microbiology College Of Natural Sciences Pusan National University

• Choi Yung

  Department Of Biochemistry Dongeui University College Of Oriental Medicine

• Lee Jae-dong

  Department Of Acupuncture & Moxibustion College Of Oriental Medicine Kyunghee University

• Jin Cheng-yun

  Department Of Microbiology College Of Natural Sciences Pusan National University

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