Induction of apoptosis in anoikis-resistant breast cancer stem cells by supercritical CO2 extracts from Citrus hassaku Hort ex Tanaka

Abstract

Anoikis (or cell-detachment-induced apoptosis) is a special form of apoptosis in which cells loose contact with other cells or the extracellular matrix. In the present study, we have found that the breast cancer stem cell line MCF-7-SC, isolated from MCF-7 breast cancer cells, shows characteristics of anoikis resistance. Treatment of supercritical CO₂ extract from Citrus hassaku Hort ex Tanaka, locally known as Phalsak, reduced the expression of ATP-binding cassette sub-family G member 2 mRNA and induced apoptosis in MCF-7-SCs, as evidenced by an increase of apoptotic body formation, increased cell population in the sub-G1 phase, increase in the Bax/Bcl-2 ratio, proteolytic activation of caspase-9 and caspase-3, and the degradation of poly(ADP-ribose) polymerase (PARP) protein. The effects of supercritical CO₂ extract from Phalsak on anoikis-resistant breast cancer stem cells suggest the use of this extract as a potential therapeutic agent for breast cancer stem cell treatment.