5-En-androstene-3 β,17 β-diol inhibits the growth of MCF-7 breast cancer cells when oestrogen receptors are blocked by oestradiol

Boccuzzi, Giuseppe; Brignardello, Enrico; Monaco, Marco Di; Gatto, V; Leonardi, Luiz Sérgio; Pizzini, A; Gallo, Marco

doi:10.1038/bjc.1994.444

Cited by 32 publications

(18 citation statements)

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“…Thus, DHEA does appear to need a 'lag-phase' before becoming active and it could be speculated that during this time it is converted into an active metabolite. Indeed, most effects of DHEA are mediated by one or other of its metabolites, such as 5-en-androsten-3β,17β diol for the hormonal effect (Boccuzzi et al, 1994) or 5-en-androsten-3β,7β,17β triol for the action on the immune system (Padgett and Loria, 1994). The active compound (i.e., DHEA or one of its metabolites) might modify the structure or lipid composition of the cell membrane.…”

Section: Discussionmentioning

confidence: 99%

Impact of Dehydroepiandrosterone in Prevention of Paracetamol Induced Nephrotoxicity in Rats

El-Karib¹

2014

American Medical Journal

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Paracetamol (PCM) overdose can cause nephrotoxicity with oxidative stress as one of the possible mechanisms mediating the event. However, Dehydroepiandrosterone (DHEA), the major secretory product of the human adrenal gland, has been shown to possess a multi-targeted antioxidant activity which is also effective against lipid peroxidation induced in various animal models and against various human disorders. In this study, the preventive effect of DHEA against PCM-induced nephrotoxicity was examined. Rats were divided into four groups containing 10 rats each, as follows: A control: Received normal saline, Vehicle treated: Received the vehicle (5% DMSO), PCM model (750 mg kg ), respectively, for 4 consecutive weeks. All treatment were given orally to animals. Our results show that co-treatment of DHEA with PCM prevented the PCM-induced nephrotoxicity and oxidative impairments of the kidney, as evidenced by a significantly reduced (p<0.05) level of serum creatinine, urea and BUN with parallel significant increases in serum protein, Cr clearance and kidneys weights. Furthermore, DHEA was able to induce a significant increment (p<0.05) of renal levels of reduced Glutathione (GSH) and activities of Superoxide Dismutase (SOD) and Glutathione Peroxidise (GPx). An effect that was accompanied with a significant decrease in renal lipid peroxides levels (MDA). The nephroprotective effects of DHEA was confirmed by a reduced intensity of renal cellular damage, as evidenced by histological findings. In conclusion, DHEA at a daily dose of 250 mg kg −1 has a protective role against PCM-induced nephrotoxicity in rats and the process is probably mediated through its antioxidant properties.

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Section: Discussionmentioning

confidence: 99%

Impact of Dehydroepiandrosterone in Prevention of Paracetamol Induced Nephrotoxicity in Rats

El-Karib¹

2014

American Medical Journal

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“…La DHEA et la 7α-hydroxy-DHEA (Chen et al, 2005 ;Martin et al, 2004) ainsi que certains dérivés androgéniques tels que le Δ5-androstène-3β,17β-diol ou le Δ5-androstane-3β,17β-diol (Adams et al, 1981 ;Boccuzzi et al, 1992 ;Boccuzzi et al, 1994 ;Guerini et al, 2005) lient le REβ. La DHEA et le Δ5-androstène-3β,17β-diol exercent des effets agonistes à faibles doses (respectivement 500nM et 2nM).…”

Section: Les Ligands Des Resunclassified

“…En effet, à faible dose, la DHEA (500nM) et son dérivé le Δ5-Androstène-3β,17β-diol (2nM), présentent des effets estrogèniques sur les cellules de carcinome mammaire MCF-7 (Adams et al, 1981 ;Boccuzzi et al, 1992 ;Boccuzzi et al, 1994 ;Guerini et al, 2005) en interagissant avec les REs.…”

Section: A Contexte Bibliographiqueunclassified

“…(Yoshida et al, 2006). La 7α-hydroxy-DHEA (Yoshida et al, 2006), l'épiandrostérone (Yoshida et al, 2006) et le Δ5-Androstène-3β,17β-diol (Adams et al, 1981 ;Boccuzzi et al, 1992 ;Boccuzzi et al, 1994 ;Guerini et al, 2005) la transactivation du REβ induite par l'E2, résultat cohérent avec une fonction antagoniste sur ce récepteur (Compton et al, 2004 ;Nuedling et al, 2001 ;Jeanes et al, 2008). Au cours d'expériences menées in vitro, la DHEA, la 7α-hydroxy-DHEA et le 5α-Androstène-3β,17β-diol lieraient également le REβ (Chen et al, 2005;Martin et al, 2004 ;Guerini V, 2005) confirmant l'importance des positions des fonctions hydroxyles et cétones des stéroïdes.…”

Section: B Objectifsunclassified

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The DHEA metabolite 7β-hydroxy-epiandrosterone exerts anti-estrogenic effects on breast cancer cell lines

et al. 2012

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Titre : La 7β-hydroxy-épiandrostérone dans des modèles in vitro de cancer du sein : effets anti-estrogéniques et rôle des récepteurs des estrogènes. La 7β-hydroxy-épiandrostérone, stéroïde endogène dérivant de la DHEA, présente des propriétés antiinflammatoires. En effet, elle module la voie des prostaglandines (PGs) en inhibant la production de la PGE2 pro-inflammatoires et en augmentant la production de la 15-Deoxy-∆ 12,14 -PGJ2 cyto-protectrice in vivo et in vitro. Les faibles doses de 7β-hydroxy-épiandrostérone (1nM, 10nM, 100nM) pour lesquelles ces effets sont observés, suggèrent une liaison à un récepteur spécifique. L'inflammation et la production des PGs jouent un rôle important dans le développement et la prolifération des tumeurs mammaires estrogéno-dépendantes. Le 17β-estradiol (E2), en se fixant sur les récepteurs des estrogènes (REs), induit la production de PGE2 et la prolifération cellulaire dans ces cellules tumorales. De ce fait, notre objectif était de tester les effets de la 7β-hydroxy-épiandrostérone sur la prolifération (comptage avec exclusion au bleu trypan), le cycle cellulaire et l'apoptose (cytométrie de flux) dans les lignées cellulaires de cancer du sein MCF-7 (REα+, REβ+, GPR30+) et MDA-MB-231 (REα-, REβ+, GPR30+) et d'identifier une(des) cible(s) potentielle(s) dans ces cellules (transactivation) et dans des cellules négatives pour les REs nucléaires SKBr3 (GPR30+) (études de prolifération). Cette étude a montré que la 7β-hydroxy-épiandrostérone exerce des effets anti-estrogéniques dans les cellules MCF-7 et MDA-MB-231 associés à une inhibition de la prolifération et un arrêt du cycle cellulaire. Les études de transactivation et de prolifération avec les agonistes spécifiques des REs ont montré une interaction avec le REβ. De plus, les résultats des études de proliférations sur les trois lignées cellulaires suggèrent que la 7β-hydroxy-épiandrostérone pourrait également interagir avec le GPR30. Ces résultats indiquent que ce stéroïde androgène agit comme un anti-estrogène. De plus, c'est la première fois qu'un stéroïde androgène à faible dose montre une action anti-proliférative dans des lignées de cancers du sein. De études ultérieures restent à réaliser afin de mieux comprendre ces effets observés. Mots clés : 7β-hydroxy-épiandrostérone, récepteurs des estrogènes, lignées de carcinomes mammaires, prolifération, transactivationThe DHEA metabolite 7β-hydroxy-epiandrosterone exerts anti-estrogenic effects on breast cancer cell lines 7β-hydroxy-epiandrosterone, an endogenous androgenic derivative of DHEA, has previously been shown to exert anti-inflammatory action in vitro and in vivo via a shift from prostaglandin E2 (PGE2) to 15-deoxy-∆ 12,14 -PGJ2 production. This modulation in prostaglandin production was obtained with low concentrations of 7β-hydroxy-epiandrosterone (1-100 nM) and suggested that it might act through a specific receptor. Inflammation and prostaglandin synthesis is important in the development and survival of estrogendependent mammary cancers. Estrogen induced PGE2 ...

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“…Liver cells have the enzymes needed to convert DHEA into a variety of steroids, including androgens, estrogens and 5-en-androsten-3b,17b-diol (ADIOL), the main DHEA metabolite that shows both androgenic and estrogenic properties (38,39).…”

Section: Discussionmentioning

confidence: 99%

Protective effect of dehydroepiandrosterone against lipid peroxidation in a human liver cell line

Gallo

Aragno

Gatto

et al. 1999

European Journal of Endocrinology

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Objective: Dehydroepiandrosterone (DHEA) is a widely studied steroid hormone with multi-functional properties. Reports suggest that some of the many activities of DHEA are due to its protective effect against lipid peroxidation. Nevertheless, the antioxidant properties of DHEA are still the subject of debate. The aim was to evaluate whether its two opposed effects on lipid peroxidation reported in the literature may be dependent on schedule and doses used. Methods: Chang liver cells, a line derived from normal human liver, were grown in media containing either no steroids (control) or DHEA at concentrations ranging from 0.1 mmol/l to 50 mmol/l. At specific times, cultures were halted and cells received a pro-oxidant stimulus (cumene (CuOOH) 0.5 mmol/l), at which time cell viability (by trypan blue staining and lactate dehydrogenase (LDH) release) and thiobarbituric acid reactive substances (TBARS) concentration (spectrophotometrical assay) were evaluated. Results: At concentrations ranging from 0.1 mmol/l to 1 mmol/l, DHEA protects Chang liver cells against lipid peroxidation and/or death induced by cumene. This effect disappears if the concentration is increased to 10 mmol/l; at higher concentrations (50 mmol/l) a pro-oxidant/cytotoxic effect of DHEA appears. Conclusions: DHEA exhibits two opposed effects on lipid peroxidation; depending on its concentration it acts either to limit or to induce oxidative stress. The threshold concentration at which the pro-oxidant activity of DHEA prevails is not far in excess of that having an antioxidant effect. Either effect of DHEA on lipid peroxidation is only evident after a 'lag-phase'.

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5-En-androstene-3 β,17 β-diol inhibits the growth of MCF-7 breast cancer cells when oestrogen receptors are blocked by oestradiol

Cited by 32 publications

References 24 publications

Impact of Dehydroepiandrosterone in Prevention of Paracetamol Induced Nephrotoxicity in Rats

Impact of Dehydroepiandrosterone in Prevention of Paracetamol Induced Nephrotoxicity in Rats

The DHEA metabolite 7β-hydroxy-epiandrosterone exerts anti-estrogenic effects on breast cancer cell lines

Protective effect of dehydroepiandrosterone against lipid peroxidation in a human liver cell line

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