Phytomedicine
Volume 13, Issue 5 , Pages 359-365, 9 May 2006

Induction of apoptosis by carbazole alkaloids isolated from Murraya koenigii

  • C. Ito

      Affiliations

    • Department of Medicinal Chemistry, Faculty of Pharmacy, Meijo University, Nagoya, Japan
    • ,
  • M. Itoigawa

      Affiliations

    • Tokai Gakuen University, Nagoya, Japan
    • Corresponding Author InformationCorresponding author. Tel.: +81528011201; fax: +81528041044.
    • ,
  • K. Nakao

      Affiliations

    • Department of Medicinal Chemistry, Faculty of Pharmacy, Meijo University, Nagoya, Japan
    • ,
  • T. Murata

      Affiliations

    • Department of Analytical Neurobiology, Faculty of Pharmacy, Meijo University, Nagoya, Japan
    • ,
  • M. Tsuboi

      Affiliations

    • Department of Analytical Neurobiology, Faculty of Pharmacy, Meijo University, Nagoya, Japan
    • ,
  • N. Kaneda

      Affiliations

    • Department of Analytical Neurobiology, Faculty of Pharmacy, Meijo University, Nagoya, Japan
    • ,
  • H. Furukawa

      Affiliations

    • Department of Medicinal Chemistry, Faculty of Pharmacy, Meijo University, Nagoya, Japan

Received 27 September 2004; accepted 9 March 2005.

Abstract 

In the current study, we isolated 10 carbazole alkaloids from the plant species Murraya koenigii (Rutaceae), and examined their effects on the growth of the human leukemia cell line HL-60. Three carbazole alkaloids, mahanine (6), pyrayafoline-D (7) and murrafoline-I (9), showed significant cytotoxicity against HL-60 cells. Fluorescence microscopy with Hoechst 33342 staining revealed that the percentage of apoptotic cells with fragmented nuclei and condensed chromatin was increased in a time-dependent manner after treatment with each alkaloid. Interestingly, each carbazole alkaloid induced the loss of mitochondrial membrane potential. In addition, both caspase-9 and caspase-3 were also time-dependently activated upon treatment with the alkaloids. Caspase-9 and caspase-3 inhibitors suppressed apoptosis induced by these alkaloids. The results suggest that these three alkaloids induced apoptosis in HL-60 cells through activation of the caspase-9/caspase-3 pathway, through mitochondrial dysfunction.

Keywords: Murraya koenigii, Rutaceae, Carbazole alkaloids, Apoptosis, HL-60 cells, Caspases

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PII: S0944-7113(05)00172-8

doi:10.1016/j.phymed.2005.03.010

Phytomedicine
Volume 13, Issue 5 , Pages 359-365, 9 May 2006

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