2. Academic Validation
  3. (-)-Syringaresinol inhibits proliferation of human promyelocytic HL-60 leukemia cells via G1 arrest and apoptosis

(-)-Syringaresinol inhibits proliferation of human promyelocytic HL-60 leukemia cells via G1 arrest and apoptosis

  • Int Immunopharmacol. 2008 Jul;8(7):967-73. doi: 10.1016/j.intimp.2008.02.012.
Bo-Young Park 1,  Sei-Ryang Oh,  Kyung-Seop Ahn,  Ok-Kyong Kwon,  Hyeong-Kyu Lee
Affiliations

Affiliation

  • 1 Natural Medicines Research Center, KRIBB, 111 Gwahangno, Yuseong-gu, Daejeon 305-806, South Korea.
PMID: 18486907 DOI: 10.1016/j.intimp.2008.02.012
Abstract

We examined the effect of (-)-syringaresinol, a furofuran-type lignan isolated from Daphne genkwa, on cell cycle regulation in HL-60 human promyelocytic leukemia cells in vitro. (-)-Syringaresinol decreased the viability of HL-60 cells by inducing G(1) arrest followed by Apoptosis in a dose- and time-dependent manner. The G(0)/G(1) phase of the cell cycle is regulated by cyclin-dependent kinases (CDK), cyclins and cyclin-dependent kinase inhibitors (Cdki). We show by western blot analysis, that the (-)-syringaresinol-induced G(1) arrest was mediated through the increased expression of Cdki proteins (p21(cip1/waf1) and p27(kip1)) with a simultaneous decrease in CDK2, CDK4, CDK6, cyclin D(1), cyclin D(2), and cyclin E expression. The induction of Apoptosis after treatment with (-)-syringaresinol for 24 h was demonstrated by morphological changes, DNA fragmentation, altered ratio of Bax/Bcl-2, cleavage of poly(ADP-ribose) polymerase and flow cytometry analysis. (-)-Syringaresinol also induced cytochrome c release and activation of Caspase-3 and caspase-9. To our knowledge, this is the first time that (-)-syringaresinol has been reported to potently inhibit the proliferation of human promyelocytic HL-60 cells through G(1) arrest and induction of Apoptosis. These findings suggest that (-)-syringaresinol may be a potential chemotherapeutic agent for the treatment of Cancer.

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