DHEA and DHEA8354 induce cellular senescence, inhibit cell proliferation and increase apoptosis in mammary tumors. (a-c) Cell proliferation in control mammary tumors (a,b) and in tumors treated with dehydroepiandrosterone (DHEA) (c). DHEA significantly decreased the proportion of bromodeoxyuridine-labeled cells (c). The slide was counterstained with hematoxylin; original magnification × 100. (d-f) DHEA-induced cellular senescence (SA-β-Gal-stained cells) in normal lobular cells (d, arrows) and in mammary tumors (e and f, arrows). (g,h) p21 and p16 were expressed in most mammary tumor cells. DHEA also induced tumor disintegration and in these areas p16 (arrows) was preferentially detected in tumor areas where SA-β-Gal-stained cells were also identified.