عنوان المقالة:β- caryophyllene, a natural sesquiterpene isolated from agar wood inhibits growth and metastasis of human colorectal cancer by modulation of multiple targets in vitro and in vivo
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.
سعد صبار دحام | Saad Sabbar Dahham | 8422