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Novel Drug Amooranin Induces Apoptosis Through Caspase Activity in Human Breast Carcinoma Cell Lines
Thangaiyan Rabi, Cheppail Ramachandran, Hugo B. Fonseca, Raveendran P.K. Nair, Arturo Alamo, Steven J. Melnick, Enrique Escalon
Amooranin (AMR) is a triterpene acid isolated from the
stem bark of a tropical tree (Amoora rohituka) grown wild
in India.
A. rohituka stem bark is one of the components
of a medicinal preparation used in the Indian Ayurvedic
system of medicine for the treatment of human malignancies.
We investigated the mechanism of cell death associated
with AMR cytotoxicity in human mammary carcinoma MCF-7,
multidrug resistant breast carcinoma MCF-7/TH and breast
epithelial MCF-10A cell lines. AMR IC50 values ranged
between 3.8-6.9 micro-g/ml among MCF-7, MCF-7/TH and MCF-10A
cells.
AMR induced oligonucleosome-sized DNA ladder formation
characteristic of apoptosis when tumor cells were treated
with 1-8 micro-g/ml AMR for 48 h. In situ cell death detection
assay indicated that AMR caused 37.3-72.1% apoptotic cells
in MCF-7, 32-48.7% in MCF-7/TH and 0-37.1% in MCF-10A
cells at 1-8 micro-g/ml concentrations.
The induction of apoptosis
in AMR treated cells was accompanied by the elevation
of total caspase and caspase-8 activities.
Flow cytometric
analysis showed that AMR induced caspase-8 activation
in 40.8-71% MCF-7, 28.5-43.2% MCF-7/TH and 4-32.8% MCF-10A
cells at 1-8 micro-g/ml concentrations.
Our results suggest
that AMR is a novel drug having potential for clinical
development against human malignancies.
[08/01/2003; Breast Cancer Research and Treatment]
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