An essential oil and its major constituent isointermedeol induce apoptosis by increased expression of mitochondrial cytochrome c and apical death receptors in human leukaemia HL-60 cells.
An essential oil from a lemon grass variety of Cymbopogon flexuosus (CFO) and its major chemical constituent sesquiterpene isointermedeol (ISO) were investigated for their ability to induce apoptosis in human leukaemia HL-60 cells because dysregulation of apoptosis is the hallmark of cancer cells. CFO and ISO inhibited cell proliferation with 48 h IC50 of approximately 30 and 20 microg/ml, respectively. Both induced concentration dependent strong and early apoptosis as measured by various end-points, e.g. annexinV binding, DNA laddering, apoptotic bodies formation and an increase in hypo diploid sub-G0 DNA content during the early 6h period of study. This could be because of early surge in ROS formation with concurrent loss of mitochondrial membrane potential observed. Both CFO and ISO activated apical death receptors TNFR1, DR4 and caspase-8 activity. Simultaneously, both increased the expression of mitochondrial cytochrome c protein with its concomitant release to cytosol leading to caspase-9 activation, suggesting thereby the involvement of both the intrinsic and extrinsic pathways of apoptosis. Further, Bax translocation, and decrease in nuclear NF-kappaB expression predict multi-target effects of the essential oil and ISO while both appeared to follow similar signaling apoptosis pathways. The easy and abundant availability of the oil combined with its suggested mechanism of cytotoxicity make CFO highly useful in the development of anti-cancer therapeutics.
Kumar
Ajay
A
Indian Institute of Integrative Medicine, Jammu, India.
Malik
Fayaz
F
Bhushan
Shashi
S
Sethi
Vijay K
VK
Shahi
Ashok K
AK
Kaur
Jagdeep
J
Taneja
Subhash C
SC
Qazi
Ghulam N
GN
Singh
Jaswant
J
D017209:Apoptosis / Q000187:drug effects*; D053181:Caspase 8 / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism; D053453:Caspase 9 / Q000187:drug effects / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D031743:Cymbopogon / Q000737:chemistry; D045304:Cytochromes c / Q000096:biosynthesis* / Q000187:drug effects; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D018922:HL-60 Cells; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000473:pathology; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D008968:Molecular Conformation; D016328:NF-kappa B / Q000096:biosynthesis / Q000187:drug effects; D009822:Oils, Volatile / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis* / Q000187:drug effects / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000096:biosynthesis* / Q000187:drug effects / Q000378:metabolism; D012717:Sesquiterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein / Q000187:drug effects / Q000378:metabolism
C494826:BAX protein, human; D016328:NF-kappa B; D009822:Oils, Volatile; D017382:Reactive Oxygen Species; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D012717:Sesquiterpenes; C105190:TNFRSF10A protein, human; D051028:bcl-2-Associated X Protein; C528862:isointermedeol; D045304:Cytochromes c; D004247:DNA; C505530:CASP8 protein, human; D053181:Caspase 8; D053453:Caspase 9