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Objective: Our study focuses upon colon cancer, due to its high rate of morbidity and mortality worldwide. Looking for new agents
from plants which are safe, available and effective have accelerated recently. We investigated the effect of β-caryophyllene (BC) on the
mechanism of cell death, inhibition of metastasis and induction of colon tumor in nude mice model.
Methods: The structure of β-caryophyllene was elucidated using FT-IR, 1H and 13C NMR and MS spectral. Anti-colon cancer
effect was investigated on HCT 116 human colorectal carcinoma cells including cytotoxicty, anti-tumorigenicity and anti-metastatic.
In addition, xenograft model was conducted in orthotopically implanted colon cancer cells in nude mice. The mechanism of the
cell death have been assessed through disruption of mitochondrial membrane potential, DNA fragmentation, ultra-structural
micrographs using (TEM) and apoptotic antibodies array.
Results: We found that BC inhibited the proliferation of colon cancer cells (median inhibitory concentration 9.5±1.0μg/ml), due
to induction of the mitochondrial pathway of apoptosis. Interestingly, the main three steps in tumor metastasis including, cell
invasion, cell migration and clonogenicity were significantly obstructed .Transmission electron microscope reveal further supportive
information on the typical singe of apoptosis morphological changes including nuclear shrinkage, chromatin condensation and
nuclear fragmentation. Administration of BC (200,100 and 50 mg/kg/day) dose-dependently inhibited the growth of colon cancer
in an orthotopic model. Tumor histology revealed significant reduction in vascularization. Bioluminescence images of implanted
tumors with pro-sense and angio-sense probes were illustrated by fluorescence molecular tomography (FMT)
Conclusion: Collectively, our results reviled a new mechanism of action of β-caryophyllene and suggest that it may be a potential
chemotherapeutic agent selectively against colon cancer.