Cytotoxicity of four Aframomum species
(A. arundinaceum, A. alboviolaceum, A. kayserianum and A.
polyanthum) towards multi-factorial drug resistant cancer cell lines
Background
The search for natural products as potential cytotoxic agents
has yielded promising candidates. However multidrug resistance (MDR) is still a
major hurdle for patients receiving chemotherapy. In the present study, we
evaluated the cytotoxicity of the methanol extracts of four dietary Aframomum plant
species (A. arundinaceum, A. alboviolaceum, A. kayserianum and A. polyanthum)
against nine sensitive and MDR cancer cell lines. We have also identified the
bioactive constituents of A. arundinaceum.
Methods
The cytotoxicity of the methanol extracts of the above plants
was determined using a resazurin reduction assay. Chromatographic techniques
were used to isolate the constituents of A. arundinaceum.
Results
A preliminary experiment on leukemia CCRF-CEM cells at
40 μg/mL showed that the extracts from A. kayserianum and A. alboviolaceum as well
as the isolated compounds namely compounds aframodial (1),
8(17),12-labdadien-15,16-dial (2), galanolactone (3),
1-p-menthene-3,6-diol
(6)
and 1,4-dimethoxybenzene (7) were less active,
inducing more than 50% growth of this cell line contrary to A. polyanthum and A. arundinaceum extracts,
galanals A (4) and B (5),
naringenin (8) and kaempferol-3,7,4’-trimethylether
(9).
The IC50 values
below or around 30 μg/mL were recorded with A. arundinaceumextract
against eight of the nine tested cancer cell lines. This extract as well as
compound 8 displayed
IC50 values
below 40 μg/mL towards the nine tested cancer cell lines whilst A. polyanthum extract,
compounds 4, 5 and 9 showed
selective activities. Collateral sensitivity (hypersensitivity) was observed
with A.
arundinaceum extract
towards leukemia CEM/ADR5000 cells and glioblastoma U87MG.ΔEGFR compared
to their respective sensitive counterparts CEM/CEM and U87MG.
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