Abstract
β-eudesmol, a natural sesquiterpenol present in a variety of Chinese herbs, is known to inhibit the proliferation of human tumor cells. However, the molecular mechanisms of the effect of β-eudesmol on human tumor cells are unknown. In the present study, we report the cytotoxic effect of β-eudesmol on the human leukemia HL60 cells and its molecular mechanisms. The cytotoxic effect of β-eudesmol on HL60 cells was associated with apoptosis, which was characterized by the presence of DNA fragmentation. β-eudesmol-induced apoptosis was accompanied by cleavage of caspase-3, caspase-9, and poly (ADP-ribose) polymerase; downregulation of Bcl-2 expression; release of cytochrome c from mitochondria; and decrease in mitochondrial membrane potential (MMP). Activation of c-Jun N-terminal kinases (JNK) mitogen-activated protein kinases was observed in β-eudesmol-treated HL60 cells, and the inhibitor of JNK blocked the β-eudesmol-induced apoptosis, downregulation of Bcl-2, and the loss of MMP. These data suggest that β-eudesmol induces apoptosis in HL60 cells via the mitochondrial apoptotic pathway, which is controlled through JNK signaling.
References
Jul 22, 1992·Biochemical Pharmacology·K SatohI Kano
Jun 5, 1992·European Journal of Pharmacology·L C Chiou, C C Chang
Aug 1, 1991·Neuropharmacology·M KimuraI Kimura
Jan 13, 1995·European Journal of Pharmacology·L C ChiouC C Chang
Aug 15, 1997·The Biochemical Journal·G M Cohen
Sep 12, 1998·Science·J M Adams, S Cory
Jun 4, 1999·Progress in Biophysics and Molecular Biology·M H Cobb
Feb 12, 2000·Molecular and Cellular Biology·K BreitschopfS Dimmeler
Mar 31, 2000·Experimental Cell Research·S B BrattonG M Cohen
Jul 27, 2000·The Journal of Biological Chemistry·M FanT C Chambers
Nov 1, 2000·Cell·R J Davis
Apr 27, 2001·The Journal of Biological Chemistry·X DengW S May
Mar 7, 2002·Developmental Cell·Guy S Salvesen, Martin Renatus
May 23, 2002·The Journal of Pharmacology and Experimental Therapeutics·Yutaro ObaraYasushi Ohizumi
Dec 12, 2002·Chemical Reviews·Jean-Bernard Denault, Guy S Salvesen
Jan 28, 2004·Cell·Nika N Danial, Stanley J Korsmeyer
Apr 21, 2005·European Journal of Pharmacology·Hiroshi TsunekiIkuko Kimura
Feb 7, 2008·Journal of Asian Natural Products Research·En-Long MaIkuko Kimura
May 20, 2009·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Enlong MaTakashi Ikejima
Jun 23, 2010·Phytotherapy Research : PTR·Eva CalviñoJosé C Diez
Jul 8, 2010·Immunopharmacology and Immunotoxicology·Min-Jun SeoHyung-Min Kim
Aug 3, 2010·Chemico-biological Interactions·Shanshan LiJianchun Li
Citations
Jun 22, 2013·Basic & Clinical Pharmacology & Toxicology·Diogo S BomfimDaniel P Bezerra
Mar 15, 2016·Journal of Oleo Science·Lotfi GhribiHichem Ben Jannet
Aug 6, 2015·Cancer Cell International·Jun MaDingfang Cai
Apr 3, 2015·Journal of Natural Medicines·Yutaka MasudaJunichi Kitajima
Sep 16, 2017·Journal of Complementary & Integrative Medicine·Wissem Aidi WannesBrahim Marzouk
Nov 20, 2016·Clinical and Experimental Pharmacology & Physiology·Na-Ra HanHyun-Ja Jeong
Jun 28, 2016·Molecular Biology Reports·Balraj Singh Gill Navgeet
Jan 26, 2017·Frontiers in Pharmacology·Minghua LiuXiukun Lin
Jun 20, 2018·BMC Pharmacology & Toxicology·Pimradasiri SrijiwangsaKesara Na-Bangchang
Jan 17, 2020·Chemistry & Biodiversity·Maria BailenAzucena Gonzalez-Coloma
Jan 16, 2021·Chemical Biology & Drug Design·Bishwanath AcharyaKesara Na-Bangchang