Abstract

 
 
 
 Purpose: To investigate the antitumor effects of ambrosin sesquiterpene lactone on drug-resistant MDA-MB-231 breast cancer cells.
 Methods: The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was used for cell viability studies. Apoptotic effects were determined using 4′,6-diamidino2-phenylindole (DAPI) staining assay, while Annexin V/PI was used for the quantification of apoptosis. Levels of reactive oxygen species (ROS) were determined by flow cytometry using DCFH-DA fluorescence staining while the effects of ambrosin on apoptosis and Wnt/beta-catenin signaling pathway-allied proteins were evaluated by Western blotting assay.
 Results: Ambrosin significantly suppressed the viability of MDA-MB-231 cells in a dose- and time-dependent manner (p < 0.05). Results from Annexin V/PI staining revealed that ambrosin induced production of apoptotic crops and blebbing of plasma membrane in MDA-MB-231 cells. Furthermore, annexin V/PI assay results showed increases in percentage of cells in different stages of apoptosis. Thus, ambrosin promoted caspase-dependent-apoptosis in MDA-MB-231 cells. Moreover, ambrosin enhanced the formation of ROS in MDA-MB-231 cells, as was evident from increased DCF- fluorescence (p < 0.05). The results also showed dose-dependent inhibition of Wnt/beta-Catenin signaling pathway by ambrosin.
 Conclusion: Ambrosin exerts a chemo-preventive effect on breast cancer cells via induction of programmed cell death, enhanced ROS production, caspase activation and suppression of Wnt/beta- catenin signaling. These findings have potential benefits for breast cancer research and drug discovery.
 
 
 
Highlights
Sesquiterpene lactones (SLs) are present in plants as secondary metabolites
The MTT assay was used to determine the effect of ambrosin on the viability of MDA-MB231 cells
The results demonstrated that ambrosin suppressed the viability of MDAMB231 Breast cancer (BC) cells in concentration and time-reliant manner
Summary
Sesquiterpene lactones (SLs) are present in plants as secondary metabolites. They contain αmethylene-γ-lactone-ring in their structures [1]. With a knowledge of the potential of ambrosin sesquiterpene, the current study was designed to investigate its effect on breast cancer cells, and its effects on programmed cell death, ROS production, caspases and the Wnt/beta-catenin signaling pathway. The cells were incubated for 24 h at 37 oC, followed by treatment with different doses of ambrosin viz 8, 16, 32 and 64 μM for 24 and 48 h. The effect of ambrosin on pro-apoptotic cell death in MDA-MB-231 cells was investigated using DAPI and annexin V/PI staining assays. Results from DAPI staining revealed marked dose-dependent increases in the number of apoptotic cells, formation of apoptotic crops, and membrane blebbing.
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