Abstract
BackgroundSeveral compounds isolated from Dryobalanops have been reported to exhibit cytotoxic effects to several cancer cell lines. This study investigated the cytotoxic effects, cell cycle arrest and mode of cell death in ampelopsin E-treated triple negative cells, MDA-MB-231.MethodsCytotoxicity of ampelopsin E, ampelopsin F, flexuosol A, laevifonol, Malaysianol A, Malaysianol D and nepalensinol E isolated from Dryobalanops towards human colon cancer HT-29, breast cancer MDA-MB-231 and MCF-7, alveolar carcinoma HeLa and mouse embryonic fibroblast NIH/3 T3 cells were determined by MTT assay. The cells were treated with the compounds (0.94–30 μM) for 72 h. The mode of cell death was evaluated by using an inverted light microscope and annexin V/PI analysis. Cell cycle analysis was performed by using a flow cytometer.ResultsData showed that ampelopsin E was most cytotoxic toward MDA-MB-231 with the IC50 (50 % inhibition of cell viability compared to control) of 14.5 ± 0.71 μM at 72 h. Cell shrinkage, membrane blebbing and formation apoptotic bodies characteristic of apoptosis were observed following treatment with ampelopsin E. The annexin V/PI flow cytometric analysis further confirmed that ampelopsin E induced apoptosis in MDA-MB-231 cells. Cell cycle analysis revealed that ampelopsin E induced G2/M phase cell cycle arrest in the cells.ConclusionAmpelopsin E induced apoptosis and cell cycle arrest in MDA-MB-231 cells. Therefore, ampelopsin E has the potential to be developed into an anticancer agent for treatment of triple negative breast cancer.
Highlights
Several compounds isolated from Dryobalanops have been reported to exhibit cytotoxic effects to several cancer cell lines
This study investigated the cytotoxic effects, cell cycle arrest and mode of cell death involved in ampelopsin E-treated triple negative cells, MDA-MB-231
Ampelopsin E was cytotoxic and inhibited growth of MDA-MB-231 cells From Table 1, ampelopsin E, Malaysianol A and flexuosol A were cytotoxic towards MDA-MB-231 cells at 14.5, 23 and 27.5 μM, while ampelopsin E was cytotoxic towards MCF-7 cells at 29.5 μM in a time- and concentration-dependent
Summary
Several compounds isolated from Dryobalanops have been reported to exhibit cytotoxic effects to several cancer cell lines. 14.1 million cancer cases and 8.2 million cancer-related deaths worldwide were recorded in 2012. Breast cancer represents a heterogeneous group of tumors with several characterizations based on their morphological and biological features, behavior and response to treatments [9]. It can be classified into different subgroups by the expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). Among all the breast cancers cases, 25 to 30 % of them are ER negative or triple negative breast cancer (TNBC) known to be most aggressive with high metastatic potential [17] especially to the vital organs such as brain and lungs. New drug for management of TNBC is in great demand
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