Eupalinin A isolated from Eupatorium chinense L. induces autophagocytosis in human leukemia HL60 cells.

Eupalinin A isolated from Eupatorium chinense L. induces autophagocytosis in human leukemia HL60 cells. Research Abstract Details 

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Eupalinin A isolated from Eupatorium chinense L. induces autophagocytosis in human leukemia HL60 cells. Abstract Text:

Tomohiro Itoh,Yuko Ito,Kenji Ohguchi,Masayoshi Ohyama,Munekazu Iinuma,Yoshinori Otsuki,Yoshinori Nozawa,Yukihiro Akao,Tomohiro Itoh,Yuko Ito,Kenji Ohguchi,Masayoshi Ohyama,Munekazu Iinuma,Yoshinori Otsuki,Yoshinori Nozawa,Yukihiro Akao,

Eupalinin A, a natural phytoalexin included in Eupatorium chinense L., exhibited a marked inhibitory effect on cell growth in HL60 cells. The morphological aspects of eupalinin A-treated cells evaluated by Hoechst 33342 nuclear staining indicated cell death, only a small part of which showed a typical apoptosis with nuclear fragmentation and condensation. To determine what type of cell death is caused by eupalinin A, we examined the contribution of caspases, Bcl-2 family proteins, MAP kinase, and PI3K/Akt, and mitochondrial membrane potential to this cell death. As a result, most part of the cell death was not associated with apoptosis because of caspase independence and no death factor released from mitochondria. Electron microscopic study indicated a characteristic finding of autophagy such as the formation of autophagosomes. Furthermore, the level of microctubule-associated-protein light chain 3 (LC3) II protein and monodancylcanaverin (MDC) incorporation were gradually increased with reduction of mitochondrial membrane potential by the accumulation of intracellular ROS after eupalinin A treatment. From these results, we can conclude that eupalinin A-induced cell death was mainly due to autophagy, which was initiated by increased ROS, resulting in the perturbation of mitochondrial membrane potential. Since the class III PI3K inhibitor such as 3-MA or LY294002 did not inhibit the eupalinin A-induced type II programmed cell death (PCD II), it was suggested that the PCD II was executed by Beclin-1 independent pathway of damage-induced mitochondrial autophagy (mitophagy).

Eupalinin A isolated from Eupatorium chinense L. induces autophagocytosis in human leukemia HL60 cells. Publishing Authors By Initials

T Itoh,Y Ito,K Ohguchi,M Ohyama,M Iinuma,Y Otsuki,Y Nozawa,Y Akao,T Itoh,Y Ito,K Ohguchi,M Ohyama,M Iinuma,Y Otsuki,Y Nozawa,Y Akao,

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Eupalinin A isolated from Eupatorium chinense L. induces autophagocytosis in human leukemia HL60 cells. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Bioorganic & medicinal chemistry

VOLUME: 16

Page Numbers: 721-31

Journal Abbreviation: Bioorg. Med. Chem.

ISSN: 1464-3391

DAY: 17

MONTH: 10

YEAR: 2007

Eupalinin A isolated from Eupatorium chinense L. induces autophagocytosis in human leukemia HL60 cells. Information

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LANGUAGE: eng

NlmUniqueID: 9413298

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AFFILIATION: Gifu International Institute of Biotechnology, 1-1 Naka-Fudogaoka, Kakamigahara, Gifu 504-0838, Japan. titoh@giib.or.jp

Country: England

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MEDLINETA: Bioorg Med Chem

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