α-Mangostin and apigenin induced the necrotic death of BT474 breast cancer cells with autophagy and inflammation
Journal Title: Asian Pacific Journal of Tropical Biomedicine - Year 2018, Vol 8, Issue 11
Abstract
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: α-Mangostin and apigenin were reported in comparison to doxorubicin, a chemotherapeutic drug. Ductal carcinoma (BT474) cell line and non-tumorigenic 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-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, the result revealed α-mangostin and apigenin were more cytotoxic to BT474 cells. Longer exposure times to α-mangostin and apigenin caused more floating cells and a lower density of adhered cells with more vacuoles present in the colonies in BT474 only. α-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, α-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, autophagy-associated and apoptosis-associated genes. Conclusions: α-Mangostin and apigenin are worth investigating as potential new sources of chemotherapeutic agents for breast cancer treatment.
Authors and Affiliations
Teeranai Ittiudomrak, Songchan Puthong, Tanapat Palaga, Sittiruk Roytrakul, Chanpen Chanchao
Keywords
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