Cytotoxic Effects of Methylgerambullin and Bis(Methylthiomethyl)-Disulphide (SB) on T-Lymphoblastic Leukemic Cell Line (Cem-SS)
The cytotoxic effects of 2 sulphur-containing compounds were studied on Tlymphoblastic leukemic cell line. Methylgerambullin is believed to be a new sulphone derived from a methylthiopropenoic acid isolated from Glycosmis calcicola (family Rutaceae). Another sui phonic compound IS bis- (methylth...
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| Format: | Thesis |
| Language: | English English |
| Published: |
2000
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| Subjects: | |
| Online Access: | http://psasir.upm.edu.my/id/eprint/8425/1/FSMB_2000_15_IR.pdf |
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| Summary: | The cytotoxic effects of 2 sulphur-containing compounds were studied on Tlymphoblastic
leukemic cell line. Methylgerambullin is believed to be a new
sulphone derived from a methylthiopropenoic acid isolated from Glycosmis
calcicola (family Rutaceae). Another sui phonic compound IS bis-
(methylthiomethyl)-disulphide, an extract from Scorodocarpus borneensis
(family Olacaceae) with irritating garlic-like odor. Cytotoxic activities of
methylgerambullin and bis-(methylthiomethyl)-disulphide were tested against
CEM-SS (T-Iymphoblastic leukaemia), KU812F (chronic myelogeneous
leukaemia), UACC-62 (melanoma) and HT29 (colon cancer) cell lines using
MTT, a colorimetric tetrazolium-based assay. Cytotoxic concentrations of the
compounds that killed cells by 50% (CD50) with respect to untreated cell
population, varied among the cell lines tested. CEM-SS was found to be the most
sensitive cell line to methylgerambullin and bis-(methylthiomethyl)-disulphide
with CD50 = 0.25 )µg/ml and 3.50 )µg/ml respectively. The cytotoxic effects
exerted by both compounds on this cell line was studied from both morphological manner over 72 hours period. Microscopic observations, including inverted
microscopy of live cultures, fluorescent microscopy of acridine orange-propidium
iodide stained cultures, and scanning and transmission electron microscopy
showed that both necrotic and apoptotic death occurred in meiliylgerambullinand
bis-(methylthiomethyl)-disulphide-treated cell populations, based on
morphological criteria. From agarose gel electrophoresis and quantitative
analyses of intemucleosomal cleavage, treatments with these compounds at their
respective CD50 doses did not yield random or multiple of 180-200 bp DNA
fragmentation which often associated with necrotic and apoptotic deaths
respectively. Such observation may simply owe to the fact that the percentage of
apoptosis and necrosis events were fairly low as quantified after acridine orangepropidium
iodide staining, or may also suggest the involvement of sulphur
residue in methylgerambullin and bis-(methylthiomethyl)-disulphide which act as
an antioxidant, thus protecting DNA degradation from occuring. Flow cytometric
analyses based on annexin V-FITC (fluorescein isothiocynate) binding to the
phosphatidylserines residue which was translocated from the inner to the outer
leaflet of the plasma membrane showed that the onset of apoptosis in both
methylgerambullin- and bis-(methylthiomethyl)-disulphide-treated population
was at 6 hours exposure. Both methylgerambullin and bis-(methylthiomethyl)disulphide
induced GO/G1 arrest up to 48 hours and 24 hours respectively
followed by arrest in the subsequent S phase. |
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