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.
ABSTRACT 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.
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ABSTRACT: The essential oils isolated from Tagetes minuta L. flowers and Ocimum basilicum L. herb were analyzed by GC/MS and assessed for antioxidant and in vitro and in vivo anticancer activities. Also biological effects of these essential oils on normal mice were studied. The major components of marigold essential oil were cis-β-ocimene (54.82%), cis-tagetone (11.50%) and trans-tagetenone (10.78%), cistagetenone (7.10%), dihydrotagetone (6.50%) and limonene (3.82%). The major components of basil essential oil were estragole (75.45%), 1,8-cineole (7.56%), linalool (5.01%), trans-anethole (3.72%) and methyleugenol (3.48%). The DPPH · scavenging activities of both essential oils were determined. 50% effective concentration (EC50) of marigold essential oil (86.35 �g/ml) was higher than basil essential oil (80.84 �g/ml). The anticancer activity of the two essential oils on two human promyelocytic leukemia cell lines (HL-60 and NB4) and experimental animals model cancer cell line (EACC) were investigated in vitro. The results indicated that the anticancer activity of marigold essential oil was higher than basil essential oil against NB4 and EACC cell lines, while basil essential oil was higher than marigold essential oil against HL-60 cell line. In in vivo study, pre-initiation treatments with the both essential oils were more effective than initiation and post-initiation treatments, respectively on the tumor (EACC) transplanted female mice. Biological effects of both essential oils on normal mice indicated that all the obtained values in all experimental animals were within the normal range.
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ABSTRACT: We investigated the apoptosis inducing effect of essential oil (EO) from aerial parts of Ocimumviride in human colorectal adenocarcinoma cells (COLO 205 cell line). The COLO 205 cells were exposed to 0.0125-0.1 microl/ml of EO for 24, 48 and 72h. Growth inhibition was determined by sulphorhodamine B (SRB) assay. Double staining with acridine orange and ethidium bromide for nuclear changes was performed. Cell cycle analysis and change in mitochondrial membrane potential was quantified by flow cytometry. Subsequently, using annexin V/PI assay, the proportion of cells actively undergoing apoptosis was determined. Changes in DNA were observed by DNA ladder assay. Eventually the surface morphology of apoptotic cells was studied by scanning electron microscopy. EO is cytotoxic to COLO 205 cells in dose and time-dependent manner, as is evident by SRB assay. This observed cell death was due to apoptosis, as established by annexin V/PI assay, DNA ladder formation and scanning electron microscopy. Our results reveal that EO has apoptosis inducing effect against COLO 205 cells in vitro and is a promising candidate for further anti-cancer study.Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 10/2009; 48(1):336-44. DOI:10.1016/j.fct.2009.10.021 · 2.61 Impact Factor
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ABSTRACT: Chlorpyrifos (CP) is a broad-spectrum organophosphorus pesticide used extensively in agricultural and domestic pest control, accounting for 50% of the global insecticidal use. In the present study, protective effects of two selenium-enriched strong antioxidative medicines IMOD and Angipars were examined in human lymphocytes treated with CP in vitro. Isolated lymphocytes were exposed to 12 µg/ml CP either alone or in combination with effective doses (ED50) of IMOD (0.2 µg/ml) and Angipars (1 µg/ml). After 3 days incubation, the viability and oxidative stress markers including cellular lipid peroxidation (LPO), myeloperoxidase (MPO), total thiol molecules (TTM), and total antioxidant power (TAP) were evaluated. Also, the levels of tumor necrosis factor-α (TNF-α), as inflammatory index along with acetylcholinesterase (AChE) activity and cell apoptosis were assessed by flow cytometry. Results indicated that effective doses of IMOD and Angipars reduced CP-exposed lymphocyte mortality rate along with oxidative stress. Both agents restored CP-induced elevation of TNF-α and protected the lymphocytes from CP-induced apoptosis and necrosis. Overall, results confirm that IMOD and Angipars reduce the toxic effects associated with CP through free radical scavenging and protection from apoptosis and necrosis.Iranian Journal of Basic Medical Science 03/2015; 18(3):284-91. · 0.60 Impact Factor