17α-androstenediol-mediated oncophagy of tumor cells by different mechanisms is determined by the target tumor.

Δ5-androstene-3β,17α-diol (17α-AED) mediates oncophagy of human myeloid, glioma, and breast tumor cells by apoptotic- and autophagic-programmed cell death pathways, whereas the 17β-epimer does not. In hematologically derived myeloid tumor cells, 17α-AED induced apoptosis, as determined by TUNEL staining, caspase, PARP activation, and electron microscopy. In contrast, 17α-AED treatment of glioma cells of neuroectodermal lineaged induced autophagy, evident by the presence of acidic vesicular organelles, LC3 processing, and upregulation of beclin-1. Proliferation inhibition studies on primary and established glioma cells demonstrated that the IC-50 of the steroid is ∼15 μM. In the case of breast cancer cells, the bioactivity of 17α-AED is independent of the expression of estrogen or androgen receptors. Collectively, oncophagy is induced by 17α-AED treatment in human tumor cells and proceeds by the induction of either autophagy or apoptosis. The neoplastic cell determines which oncophagic pathway is utilized.