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Full Length Research Paper
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Cytotoxic effect of 2’,
3’-epoxy isocapnolactone and
8-hydroxyisocapnolactone-2’3’-diol isolated from
Micromelum minutum (G.Forst.) Wight and Arn. in human
T-lymphocyte leukemia CEM-SS cells
B. K. Tan1, N. B. Alitheen1*,
S. K. Yeap2, A. M. Ali3 and R. Mawardi4
1Institute
of Bioscience, University Putra Malaysia, 43400 Serdang,
Selangor, Malaysia.
2Department
of Cell and Molecular Biology, Faculty of Biotechnology and
Biomolecular Sciences, University Putra Malaysia, 43400
Serdang, Selangor, Malaysia.
3Faculty
of Agriculture and Biotechnology, University Darul Iman
Malaysia (UDM), Kampus Kota, Jalan Sultan Mahmud, 20400
Kuala Terengganu, Malaysia.
4Department
of Chemistry, Faculty of Science, University Putra Malaysia,
43400 Serdang, Selangor, Malaysia.
*Corresponding author. E-mail:
noorjahan@biotech.upm.edu.my.
Tel.: 603 89477471. Fax: 603 89747510.
Accepted 4 May, 2009 |
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Abstract |
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2’,3’-Epoxyisocapnolactone and
8-hydroxyisocapnolactone-2’,3’-diol are two bioactive
compounds isolated from the leaves of Micromelum minutum.
In
this study, the induction of apoptosis by
2’,3’-epoxyisocapnolactone and
8-hydroxyisocapnolactone-2’,3’-diol on CEM-SS cells were
investigated. The cytotoxicity of
2’,3’-epoxyisocapnolactone and
8-hydroxyisocapnolactone-2’,3’-diol was screened on CEM-SS
by using MTT assay. The apoptotic effect of both compounds
on CEM-SS was evaluated by using fluorescence and
electron microcopies morphological observation and
DNA laddering analysis.
The inhibition effect of
2’,3’-epoxyisocapnolactone and
8-hydroxyisocapnolactone-2’,3’-diol at 50% of cell
population (IC50) was found to be 4.6
µg/ml (13.5 µM) and 3 µg/ml (7.8 µM) on CEM-SS cells,
respectively. From DNA
fragmentation, Acridine orange and
Propidium iodide
staining and electron microscope analyses, the compounds
were confirmed to have ability in promoting apoptosis.
However, the % of apoptosis induced is low and the event is
time-dependent. At high concentration of 10 µg/mL,
2’,3’-epoxyisocapnolactone and
8-hydroxyisocapnolactone-2’,3’-diol induced necrosis.
Furthermore,
8-hydroxyisocapnolactone-2’,3’-diol also exhibited
better cytotoxicity compared to
2’,3’-epoxyisocap-nolactone. The induction time for
apoptosis by
8-hydroxyisocapnolactone-2’,3’-diol in CEM-SS is
earlier than
2’,3’-epoxyisocapnolactone, which is 4 h and 12 h
after treatment. Both
2’,3’-epoxyisocapnolactone and
8-hydroxyisocapnolactone-2’,3’-diol are potential as
anticancer agent.
Key
words:
Cytotoxic, 2’,3’-epoxy isocapnolactone,
8-hydroxyisocapnolactone-2’3’-diol, Micromelum minutum,
CEM-SS. |
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