Abstract
Terpinen-4-ol, a monoterpene, is found as the main component of essential oil extracts from many plants. In this study apoptotic and autophagic types of cell death induced by terpinen-4-ol and associated mechanisms were investigated in human leukemic HL-60 cells. The cytotoxicity of human leukemic U937 and HL-60 cells was determined by MTT assay. Cytochrome c release, expression of Bax, Bcl-2, Bcl-xl and cleaved Bid were determined by Western blotting. Cell morphology was examined under a transmission electron microscope. LC3-I/II, ATG5 and Beclin-1 levels were detected by immunoblotting. Terpinen-4-ol exhibited cytotoxicity to human leukemic HL-60 but not U937 cells. The apoptotic response to terpinen-4-ol in HL-60 cells was due to induction of cytochrome c release from mitochondria and cleavage of Bid protein after the stimulation of caspase-8. There was a slightly decrease of Bcl-xl protein level. The characteristic cell morphology of autophagic cell death was demonstrated with multiple autophagosomes in the cytoplasm. At the molecular level, the results from Western blot analysis showed that terpinen-4-ol significantly induced accumulation of LC3-I/II, ATG5 and Beclin-1, regulatory proteins required for autophagy in mammalian cells. Terpinen-4-ol induced-human leukemic HL-60 cell death was via both autophagy and apoptosis.
Highlights
Apoptosis is a form of cellular suicide that is essential for development and tissue homeostasis of all multicellular organisms
Percent cell viability of HL-60 and MOLT-4 cells were reduced by terpinen-4-ol with a dose-dependence manner, whereas terpinen-4-ol had no cytotoxic effect on U937 as shown in Figure 1 and our previous report (Khaw-on and Banjerdpongchai, 2012)
Since the cytotoxicity of cancer cells can be caused by reactive oxygen species (ROS), HL-60 cells treated with terpinen-4-ol were determined for ROS generation by using DCFH2-DA and flow cytometry
Summary
Apoptosis is a form of cellular suicide that is essential for development and tissue homeostasis of all multicellular organisms. The integrity of mitochondrial membranes is primarily controlled by a balance between the antagonistic actions of the proapoptotic and anti-apoptotic members of the Bcl-2 family (Lewis et al, 2005). In this study apoptotic and autophagic types of cell death induced by terpinen-4-ol and associated mechanisms were investigated in human leukemic HL-60 cells. Results: Terpinen-4-ol exhibited cytotoxicity to human leukemic HL-60 but not U937 cells. The apoptotic response to terpinen-4-ol in HL-60 cells was due to induction of cytochrome c release from mitochondria and cleavage of Bid protein after the stimulation of caspase-8. The results from Western blot analysis showed that terpinen-4-ol significantly induced accumulation of LC3-I/II, ATG5 and Beclin-1, regulatory proteins required for autophagy in mammalian cells. Conclusions: Terpinen-4-ol induced-human leukemic HL-60 cell death was via both autophagy and apoptosis
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
