Abstract
BackgroundClausena excavata Burm.f. is a shrub traditionally used to treat cancer patients in Asia. The main bioactive chemical components of the plant are alkaloids and coumarins. In this study, we isolated clausenidin from the roots of C. excavata to determine its apoptotic effect on the colon cancer (HT-29) cell line.MethodWe examined the effect of clausenidin on cell viability, ROS generation, DNA fragmentation, mitochondrial membrane potential in HT-29 cells. Ultrastructural analysis was conducted for morphological evidence of apoptosis in the treated HT-29 cells. In addition, we also evaluated the effect of clausenidin treatment on the expression of caspase 3 and 9 genes and proteins in HT-29 cells.ResultClausenidin induced a G0/G1 cell cycle arrest in HT-29 cells with significant (p < 0.05) dose-dependent increase in apoptotic cell population. The DNA fragmentation assay also showed apoptotic features in the clausenidin-treated HT-29 cells. Clausenidin treatment had caused significant (p < 0.05) increases in the expression of caspase 9 protein and gene in HT-29 cells and mitochondrial ROS and mitochondrial membrane depolarization. The results suggest the involvement of the mitochondria in the caspase-dependent apoptosis in clausenidin-treated colon cancer cells.ConclusionClausenidin induces a caspase-dependent apoptosis in colon cancers through the stimulation of the mitochondria. The study demonstrates the potential of clausenidin for use in the treatment of colon cancers.
Highlights
Clausena excavata Burm.f. is a shrub traditionally used to treat cancer patients in Asia
The results suggest the involvement of the mitochondria in the caspase-dependent apoptosis in clausenidin-treated colon cancer cells
The current study describes for the first time, some molecular mechanisms involved in clausenidin-induced cell death in a colon cancer cell line
Summary
Clausena excavata Burm.f. is a shrub traditionally used to treat cancer patients in Asia. It has been shown that there are close associations between molecular signaling, energy generation, and proliferation of tumors [4, 5] Since these molecular mechanisms can Cancer chemotherapeutic agents are screened and selected based on their potentials to induce apoptosis [7]. Apoptosis is an integral cell death program characterized by DNA fragmentation as well as loss of mitochondrial membrane integrity [8]. This mode of cell death is driven by caspases and proceeds via the extrinsic or intrinsic pathways. A comparison between the normal and tumor cells of colorectal cancer patients had shown decreased expression of caspase 9 in tumors [14]. In situations where tumors arise due to altered gene expression, treatments can be targeted towards improving the expression of the gene because the activation or inhibition of certain genes could stimulate apoptosis and alter the kinetics of tumor growth [15]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
