title: 17α-androstenediol-mediated oncophagy of tumor cells by different mechanisms is determined by the target tumor.
abstract: 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.
authors: Department of Microbiology and Immunology, Virginia Commonwealth University Medical Center, Richmond, Virginia, USA. loria@vcu.edu
authors: Roger M
authors: RM
authors: Loria
authors: Martin R
authors: MR
authors: Graf
mesh_terms: D015114:Androstenediol / Q000737:chemistry / Q000494:pharmacology*; D018931:Antineoplastic Agents, Hormonal / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001343:Autophagy / Q000187:drug effects* / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D018931:Antineoplastic Agents, Hormonal; D015114:Androstenediol