One size does not fit all: An in vitro evaluation of the effects of bezafibrate and medroxyprogesterone acetate on human SH-SY5Y and U-87 MG cancer cells

Here, we have examined the effects of the repurposed drugs bezafibrate (BEZ) and medroxyprogesterone acetate (MPA) singly and in combination (BaP) on a neuroblastoma (SH-SY5Y) and a glioblastoma (U-87 MG) cell line. BaP was previously shown to inhibit the growth of blood and bone cancers through the generation of reactive oxygen species (ROS) and by targeting lipogenesis. Similarly, in our study, BaP inhibited cell proliferation and induced cell death in both neuroblastoma and glioblastoma cells more effectively than single BEZ or MPA drug treatments, albeit less effectively than in blood cancers. Furthermore, we observed significant increases in ROS levels in both cancer cell lines and reductions in the levels of the lipogenic enzyme, stearoyl-CoA-desaturase 1 (SCD1). Supplementation with the SCD1 product, oleic acid (OA), moderately abrogated the inhibitory effects of BaP on neuroblastoma proliferation. However, this effect was not seen in glioblastoma cultures, where OA supplementation of BaP-treated cells was associated with further decreases in cell proliferation. Lastly, we show that a clinically achievable BaP concentration enhanced the antiproliferative effects of temozolomide on glioblastoma cells. These findings show that drugs that have been successfully repurposed to potentially treat some types of cancers may have use in other cancers, but that their efficacy and mechanisms of action do not necessarily translate from one cancer type to another. Thus, successful drug repurposing requires investigation and optimisation on a case-by-case basis.