a-Mangostin and apigenin induced the necrotic death of BT474 breast cancer cells with autophagy and inflammation
Objective: To find new compounds in order to overcome the mainstay of metastatic breast cancer due to the adverse side effects from, and increasing resistance to, current chemotherapeutic agents. Methods:a-Mangostin and apigenin were reported in comparison to doxorubicin, a chemotherapeutic drug. Ductal carcinoma (BT474) cell line and nontumorigenic epithelial tissue from mammary gland (MCF-10A) were used. Cell viability assessment was calculated by the standard 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. Cell morphology was investigated by light microscopy. By flow cytometry analysis, programmed cell death was observed using annexin V and propidium iodide staining while cell-cycle arrest was observed using propidium iodide staining. Change in transcriptional expression was evaluated by real-time quantitative reverse transcription PCR. Results: In 3-(4,5dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, the result revealed a-mangostin and apigenin were more cytotoxic to BT474 cells. Longer exposure times to a-mangostin and apigenin caused more floating cells and a lower density of adhered cells with more vacuoles present in the colonies in BT474 only. a-Mangostin and apigenin caused necrosis in BT474 cells in a 24 h exposure, but a small amount of early apoptotic cells could also be detected at 24, 48 and 72 h exposure, whereas doxorubicin caused early apoptosis to BT474 cells at 24 h. Transcript expression and activity analysis supported caspase-3 was involved in the death of BT474 cells treated by all compounds. Moreover, a-mangostin and apigenin arrested the cell-cycle at the G1-phase, but at the G2/M-phase by doxorubicin. All three compounds induced a change in transcript expression levels of inflammation-associated, proto-oncogene, autophagyassociated and apoptosis-associated genes. Conclusions:a-Mangostin and apigenin are worth investigating as potential new sources of chemotherapeutic agents for breast cancer treatment.
Ittiudomrak T, Puthong S, Palaga T, Roytrakul S, Chanchao C. a-Mangostin and apigenin induced the necrotic death of BT474 breast cancer cells with autophagy and inflammation. Asian Pac J Trop Biomed 2018; 8(11): 519-526.