Contribution of α2-adrenoceptors to the mitogenic effect of catecholestrogen in human breast cancer MCF-7 cells

Chiesa, Ignacio Javier; Castillo, Luciana Andrea; Lüthy, Isabel Alicia

doi:10.1016/j.jsbmb.2008.03.035

Cited by 14 publications

(6 citation statements)

References 32 publications

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“…1, panel b). It can be concluded from this work that 2 -AR contribute at least in part to the mitogenic effect of 2-OH-E 2 , 2-OH-E 1 and 4-OH-E 1 [57]. When comparing the molecular structures of the natural catecholamines (Fig.…”

Section: -And 2 -Adrenoceptors Breast/mammary Structuresmentioning

confidence: 71%

“…We have then studied if the proliferative action of catecholestrogens in breast cancer cells could be mediated by the 2 -AR [57]. In mammalian species, catecholestrogen formation from E 2 is quantitatively the most important metabolic pathway of this endogenous sex hormone, rivaling the parent estrogens in concentration [58].…”

Section: -And 2 -Adrenoceptors Breast/mammary Structuresmentioning

confidence: 99%

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Adrenoceptors: Non Conventional Target for Breast Cancer?

Lüthy¹,

Bruzzone²,

Piñero³

et al. 2009

CMC

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Epinephrine and Norepinephrine, typically released during stress bind to nine different adrenoceptors (AR) which classically control the cardiovascular and respiratory systems. New targets were described for the many agonists and antagonists developed for these AR, as the central nervous system. During the last three decades, AR expression and action on the mammary gland/breast were extensively investigated. In the cow mammary gland, good milkability was associated with low density of beta(2)-AR and high density of alpha(2)-AR. In the rat normal mammary gland, beta-AR are expressed in the epithelial cells, alveoli, ducts, and adipocytes showing an exquisite regulation by steroid hormones and prolactin. In rat dimethylbenz(a)anthracene (DMBA) tumors, a close correlation was observed between tumor growth and beta-AR concentration. beta(2)-AR were described in numerous human cell lines and breast tumors. The action of beta-adrenergic compounds on cell proliferation is contradictory. While some authors found that beta-agonists significantly inhibit cancer cell proliferation and tumor growth in mice, others described a significant reduction in DNA synthesis by beta-blockers. Also, positive effects of beta-AR on human carcinoma cell migration have been described. alpha(2)-AR are expressed in human breast cancer and non-cancer cell lines, their stimulation being associated with increased cell proliferation. In vivo clonidine increased tumor growth and alpha (2)-adrenergic antagonists completely reversed this effect. When administered alone, rauwolscine inhibited tumor growth behaving as an inverse agonist. Therefore, the numerous adrenergic beta- and alpha-AR agonists or antagonists could prove to be unexpected therapeutic options for mammary gland/ breast and mainly breast cancer.

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Section: -And 2 -Adrenoceptors Breast/mammary Structuresmentioning

confidence: 71%

Section: -And 2 -Adrenoceptors Breast/mammary Structuresmentioning

confidence: 99%

Adrenoceptors: Non Conventional Target for Breast Cancer?

Lüthy¹,

Bruzzone²,

Piñero³

et al. 2009

CMC

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“…The bioactivation of estrogens into catechol-estrogens such as hydroxy-estrogens through CYPs have been shown to increase proliferation of cells [24,25] and associate with tumors including prostate [9,26]. These forms of estrogen can subsequently lead to the formation of semi-quinones and quinones that are known to react with DNA [27,28].…”

Section: Discussionmentioning

confidence: 99%

Suppressor effect of catechol-O-methyltransferase gene in prostate cancer

et al. 2021

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Catechol-estrogens can cause genetic mutations and to counteract their oncogenicity, the catechol-O-methyltransferase (COMT) gene is capable of neutralizing these reactive compounds. In this study, we determined the functional effects and regulation of COMT in prostate cancer. Both the Cancer Genome Atlas (TCGA) and immunohistochemical analysis of clinical specimens demonstrated a reduction of COMT expression in prostate cancer. Also, western analyses of prostate cancer cell lines show COMT levels to be minimal in DuPro and DU145 and thus, these cells were used for further analyses. Re-expression of COMT led to suppressed migration ability (wound healing assay) and enhanced apoptosis (flow cytometric analyses), and when challenged with 4-hydroxyestradiol, a marked reduction of cell proliferation (MTT assay) was observed. Xenograft growth in athymic mice also resulted in inhibition due to COMT. As a mechanism, western analyses show cleaved CASP3 and BID were increased whereas XIAP and cIAP2 were reduced due to COMT. As COMT expression is low in prostate cancer, its regulation was determined. Databases identified several miRNAs capable of binding COMT and of these, miR-195 was observed to be increased in prostate cancer according to TCGA. Real-time PCR validated upregulation of miR-195 in clinical prostate cancer specimens as well as DuPro and DU145 and interestingly, luciferase reporter showed miR-195 capable of binding COMT and overexpressing miR-195 could reduce COMT in cells. These results demonstrate COMT to play a protective role by activating the apoptosis pathway and for miR-195 to regulate its expression. COMT may thus be a potential biomarker and gene of interest for therapeutic development for prostate cancer.

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“…Although only α 1 -adrenoreceptors have been reported to participate in liver regeneration, the observed inhibitory effect by SB-269970 could also be attributed to α 2 -receptor blockade especially since α 2 -adrenoreceptors are expressed in hepatocytes [ 42 , 43 ]. Activation of α 2 -adrenergic receptors has been reported to induce cell proliferation in different cell types [ 44 - 46 ], whereas competitive inhibition of these receptors attenuates cell proliferation and/or induces apoptosis [ 44 , 45 , 47 ]. However, there are reports that connect α 2 -receptor stimulation with inhibition of cell growth [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

Effect of 5-HT7receptor blockade on liver regeneration after 60-70% partial hepatectomy

Tzirogiannis¹,

Kourentzi²,

Zyga

et al. 2014

BMC Gastroenterol

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BackgroundSerotonin exhibits a vast repertoire of actions including cell proliferation and differentiation. The effect of serotonin, as an incomplete mitogen, on liver regeneration has recently been unveiled and is mediated through 5-HT2 receptor. The aim of the present study was to investigate the effect of 5-HT7 receptor blockade on liver regeneration after partial hepatectomy.MethodsMale Wistar rats were subjected to 60-70% partial hepatectomy. 5-HT7 receptor blockade was applied by intraperitoneal administration of SB-269970 hydrochloride two hours prior to and sixteen hours after partial hepatectomy and by intraperitoneal administration of SB-258719 sixteen hours after partial hepatectomy. Animals were sacrificed at different time points until 72 h after partial hepatectomy. Liver regeneration was evaluated by [3H]-thymidine incorporation into hepatic DNA, the mitotic index in hematoxylin-eosin (HE) sections and by immunochemical detection of Ki67 nuclear antigen. Reversion of 5-HT7 blockade was performed by intraperitoneal administration of AS-19. Serum and liver tissue lipids were also quantified.ResultsLiver regeneration peaked at 24 h ([3H]-thymidine incorporation into hepatic DNA and mitotic index by immunochemical detection of Ki67) and at 32 h (mitotic index in HE sections) in the control group of rats. 5-HT7 receptor blockade had no effect on liver regeneration when applied 2 h prior to partial hepatectomy. Liver regeneration was greatly attenuated when blockade of 5-HT7 receptor was applied (by SB-258719 and SB-269970) at 16 h after partial hepatectomy and peaked at 32 h ([3H]-thymidine incorporation into hepatic DNA and mitotic index by immunochemical detection of Ki67) and 40 h (mitotic index in HE sections) after partial hepatectomy. AS-19 administration totally reversed the observed attenuation of liver regeneration.ConclusionsIn conclusion, 5-HT7 receptor is a novel type of serotonin receptor implicated in hepatocyte proliferation.

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Contribution of α2-adrenoceptors to the mitogenic effect of catecholestrogen in human breast cancer MCF-7 cells

Cited by 14 publications

References 32 publications

Adrenoceptors: Non Conventional Target for Breast Cancer?

Adrenoceptors: Non Conventional Target for Breast Cancer?

Suppressor effect of catechol-O-methyltransferase gene in prostate cancer

Effect of 5-HT7receptor blockade on liver regeneration after 60-70% partial hepatectomy

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