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17α‐androstenediol‐mediated oncophagy of tumor cells by different mechanisms is determined by the target tumor
Author(s) -
Loria Roger M.,
Graf Martin R.
Publication year - 2012
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2012.06602.x
Subject(s) - autophagy , apoptosis , cancer research , downregulation and upregulation , androstenediol , glioma , chemistry , tunel assay , programmed cell death , organelle , biology , myeloid , microbiology and biotechnology , androgen , biochemistry , gene , hormone , androstenedione
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.