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17. Localization and regulation of aromatase liver receptor homologue-1 in the developing rat testis.

Author

Clyne C.D., Poobalan Y., Meachem S.J., Knower K., Young M.J., Sirianni R., Pezzi V., Sierens J., Jakody I., Clyne C.D., Poobalan Y., Meachem S.J., Knower K., Young M.J., Sirianni R., Pezzi V., Sierens J., and Jakody I.

Abstract

The enzyme aromatase converts androgens to estrogens, which have recently been postulated to be essential for testicular development and fertility. Understanding the mechanisms that regulate aromatase activity in the testis may therefore have implications for treatment of male infertility. Aromatase is encoded by the CYP19 gene, which uses multiple tissue-specific alternative promoters. In the testis, the proximal promoter PII drives aromatase expression. PII activity requires a nuclear receptor half-site, CAAGGTCA, to which two orphan receptors; SF-1 and LRH-1, have been shown to bind in vitro. The aim of this study was to investigate expression of aromatase and LRH-1 in the developing rat testis and define the ability of LRH-1 to induce aromatase expression in the testicular cells where both are expressed. We show that aromatase and LRH-1 are present throughout all stages of development of the rat testis, although the sites and levels of expression vary. The pattern of LRH-1 expression was broadly similar to that of aromatase. In adult animals higher levels of expression were observed in Leydig and germ cells. Over-expression of LRH-1 in primary rat Leydig and germ cells by adenoviral infection strongly increased endogenous aromatase mRNA levels, demonstrating the ability of LRH-1 to stimulate aromatase expression in vivo. We also observed binding of endogenous LRH-1 to the aromatase promoter II by chromatin immunoprecipitation. These data provide evidence that LRH-1 plays an important role in the regulation of testicular aromatase expression, and implicate LRH-1 as a regulator of rat spermatogenesis, in which estrogens are emerging as important mediators. © 2010 Elsevier Ireland Ltd.

Published
2015

20. Endemic goiter in Calabria:etiopathogenesis and thyroid function

Author

ANDO' S, MAGGIOLINI M, DI CARLO A, DIODATO A, BLOISE A, DE LUCA GP, PEZZI V, SISCI D, MARIANO A, MACCHIA, VINCENZO, Ando', S, Maggiolini, M, DI CARLO, A, Diodato, A, Bloise, A, DE LUCA, Gp, Pezzi, V, Sisci, D, Mariano, A, and Macchia, Vincenzo

Published
1994

38. G-protein-coupled receptor 30 and estrogen receptor-[alpha] are involved in the proliferative effects induced by atrazine in ovarian cancer cells.

Author

Albanito L, Lappano R, Madeo A, Chimento A, Prossnitz ER, Cappello AR, Dolce V, Abonante S, Pezzi V, and Maggiolini M

Abstract

BACKGROUND: Atrazine, one of the most common pesticide contaminants, has been shown to up-regulate aromatase activity in certain estrogen-sensitive tumors without binding or activating the estrogen receptor (ER). Recent investigations have demonstrated that the orphan G-protein--coupled receptor 30 (GPR30), which is structurally unrelated to the ER, mediates rapid actions of 17ß-estradiol and environmental estrogens. OBJECTIVES: Given the ability of atrazine to exert estrogen-like activity in cancer cells, we evaluated the potential of atrazine to signal through GPR30 in stimulating biological responses in cancer cells. METHODS AND RESULTS: Atrazine did not transactivate the endogenous ER[alpha] in different cancer cell contexts or chimeric proteins encoding the ER[alpha] and ERß hormone-binding domain in gene reporter assays. Moreover, atrazine neither regulated the expression of ER[alpha] nor stimulated aromatase activity. Interestingly, atrazine induced extracellular signal-regulated kinase (ERK) phosphorylation and the expression of estrogen target genes. Using specific signaling inhibitors and gene silencing, we demonstrated that atrazine stimulated the proliferation of ovarian cancer cells through the GPR30--epidermal growth factor receptor transduction pathway and the involvement of ER[alpha]. CONCLUSIONS: Our results indicate a novel mechanism through which atrazine may exert relevant biological effects in cancer cells. On the basis of the present data, atrazine should be included among the environmental contaminants potentially able to signal via GPR30 in eliciting estrogenic action. [ABSTRACT FROM AUTHOR]

Published
2008
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40. Synthesis and in Vitro and in Vivo Antitumor Activity of 2-Phenylpyrroloquinolin-4-ones

Author

Ferlin, M. G., Chiarelotto, G., Gasparotto, V., Via, L. Dalla, Pezzi, V., Barzon, L., Palu, G., and Castagliuolo, I.

Abstract

In our search for potential new anticancer drugs, we designed and synthesized a series of tricyclic compounds containing the antimitotic 2-phenylazaflavone chromophore fused to a pyrrole ring in a pyrroloquinoline structure. Compounds 8, 18, 19, 22, 23, 25 and 26, when tested against a panel of fourteen human tumor cell lines, showed poor in vitro cytotoxic activity, whereas 20, 21 and 24 showed significant activity (IC50 0.7 to 50 μM). Steroid hormone-sensitive ovary, liver, breast and adrenal gland adenocarcinoma cell lines displayed the highest sensitivity (IC50 0.7 to 8 μM). Compound 24 blocked cells in the G2/M phase of the cell cycle and induced a significant increase in apoptotis. Compounds 20, 21 and 24 proved to alter microtubule assembly and stability, displaying a cytoplasmic microtubule network similar to that caused by Vincristine. In vivo, administration of compound 24 to Balb/c mice inhibited the growth of a syngenic hepatocellular carcinoma.

Published
2005

47. Retraction: G-Protein-Coupled Receptor 30 and Estrogen Receptor-α Are Involved in the Proliferative Effects Induced by Atrazine in Ovarian Cancer Cells.

Author

Albanito, L., Lappano, R., Madeo, A., Chimento, A., Prossnitz, E. R., Cappello, A. R., Dolce, V., Abonante, S., Pezzi, V., and Maggiolini, M.

Subjects
SERIAL publications
Abstract

A retraction of the article "G-Protein–Coupled Receptor 30 and Estrogen Receptor-α Are Involved in the Proliferative Effects Induced by Atrazine in Ovarian Cancer Cells" by L. Albanito, R. Lappano, A. Madeo, A. Chimento, E. R. Prossnitz, A. R. Cappello, V. Dolce, S. Abonante, V. Pezzi, and M. Maggiolini that appeared in the February 1, 2014 issue is presented.

Published
2014
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48. Synthesis and cytotoxic activity evaluation of 2,3-thiazolidin-4-one derivatives on human breast cancer cell lines

Author

Carmela Saturnino, Alessia Bertamino, Rosa Sirianni, Ciro Milite, Pietro Campiglia, Simona Musella, Adele Chimento, Maria Stefania Sinicropi, Ettore Novellino, Vincenzo Pezzi, Marina Sala, Anna Caruso, Paolo Tortorella, Isabel Gomez-Monterrey, Sala, M, Chimento, A, Saturnino, C, GOMEZ MONTERREY, ISABEL MARIA, Musella, S, Bertamino, A, Milite, C, Sinicropi, M, Caruso, A, Sirianni, R, Tortorella, P, Novellino, Ettore, Campiglia, P, and Pezzi, V.

Subjects
Clinical Biochemistry, Pharmaceutical Science, Breast Neoplasms, Pharmacology, Resveratrol, Biochemistry, chemistry.chemical_compound, Cell Line, Tumor, Drug Discovery, Stilbenes, medicine, Cytotoxic T cell, Humans, skin and connective tissue diseases, Molecular Biology, Cell Proliferation, Chemistry, Organic Chemistry, Cancer, medicine.disease, Antineoplastic Agents, Phytogenic, Bioavailability, MCF-7, Polyphenol, SKBR3, Molecular Medicine, Female, Thiazolidinediones, Drug Screening Assays, Antitumor, Human breast
Abstract

It is well known that resveratrol (RSV) displayed cancer-preventing and anticancer properties but its clinical application is limited because of a low bioavailability and a rapid clearance from the circulation. Aim of this work was to synthesize pharmacologically active resveratrol analogs with an enhanced structural rigidity and bioavailability. In particular, we have synthesized a library of 2,3-thiazolidin-4-one derivatives in which a thiazolidinone nucleus connects two aromatic rings. Some of these compounds showed strong inhibitory effects on breast cancer cell growth. Our results indicate that some of thiazolidin-based resveratrol derivatives may become a new potent alternative tool for the treatment of human breast cancer.

Published
2013

49. Biological activity of 3-chloro-azetidin-2-one derivatives having interesting antiproliferative activity on human breast cancer cell lines

Author

Carmela Saturnino, Ortensia Ilaria Parisi, Francesco Puoci, Adele Chimento, Rosa Sirianni, Maria Stefania Sinicropi, Ettore Novellino, Alessia Bertamino, Vincenzo Pezzi, Marina Sala, Anna Caruso, Emilia Martire, Isabel Gomez-Monterrey, Simona Musella, Carmela Campana, Pietro Campiglia, Chimento, A, Sala, M, GOMEZ MONTERREY, ISABEL MARIA, Musella, S, Bertamino, A, Caruso, A, Sinicropi, M, Sirianni, R, Puoci, F, Parisi, Oi, Campana, C, Martire, E, Novellino, Ettore, Saturnino, C, Campiglia, P, and Pezzi, V.

Subjects
Clinical Biochemistry, Pharmaceutical Science, Breast Neoplasms, Resveratrol, Biochemistry, chemistry.chemical_compound, Mice, Breast cancer, Cell Line, Tumor, Drug Discovery, Stilbenes, medicine, Animals, Humans, Molecular Biology, Cell Proliferation, Chemistry, Organic Chemistry, food and beverages, Cancer, Biological activity, 3T3 Cells, medicine.disease, Antineoplastic Agents, Phytogenic, Bioavailability, MCF-7, SKBR3, Polyphenol, MCF-7 Cells, Molecular Medicine, Azetidines, Female
Abstract

Resveratrol (3,4',5 tri-hydroxystilbene), a natural plant polyphenol, has gained interest as a non-toxic agent capable of inducing tumor cell death in a variety of cancer types. However, therapeutic application of these beneficial effects remains very limited due to its short biological half-life, labile properties, rapid metabolism and elimination. Different studies were undertaken to obtain synthetic analogs of resveratrol with major bioavailability and anticancer activity. We have synthesized a series 3-chloro-azetidin-2-one derivatives, in which an azetidinone nucleus connects two aromatic rings. Aim of the present study was to investigate the effects of these new 3-chloro-azetidin-2-one resveratrol derivatives on human breast cancer cell lines proliferation. Our results indicate that some azetidin-based resveratrol derivatives may become new potent alternative tools for the treatment of human breast cancer.

Published
2013

50. A new role of anandamide in human sperm: focus on metabolism

Author

Carmela Guido, Sebastiano Andò, Antonietta Santoro, Saveria Aquila, Maurizio Bifulco, Vincenzo Pezzi, Salvatore Panza, Chiara Laezza, Aquila, S, Guido, C, Laezza, C, Santoro, A, Pezzi, V, Panza, S, Andò, S, and Bifulco, M.

Subjects
Male, medicine.medical_specialty, Cannabinoid receptor, Polyunsaturated Alkamides, Physiology, Clinical Biochemistry, Intracellular Space, Arachidonic Acids, Biology, Acyl-CoA Dehydrogenase, chemistry.chemical_compound, Capacitation, Internal medicine, Insulin Secretion, medicine, Humans, Insulin, Phosphorylation, Phosphotyrosine, Triglycerides, Sperm motility, urogenital system, Proteins, Tyrosine phosphorylation, Lipid metabolism, Lipase, Cell Biology, Anandamide, Spermatozoa, Sperm, Endocannabinoid system, Glucose, Endocrinology, chemistry, Sperm Motility, Calcium, lipids (amino acids, peptides, and proteins), Endocannabinoids
Abstract

The endocannabinoid system and the presence of CB1 receptor (CB1-R) target of the anandamide were identified in human sperm, however the anandamide action in this context needs to be further elucidated. At this purpose we analyzed the effects of anandamide on human sperm capacitation and motility. Afterwards, we focused on lipid and glucose sperm metabolism and also investigated the interrelationship between anandamide and insulin secretion by sperm. By intracellular free Ca(2+) content assay and proteins tyrosine phosphorylation, we evidenced that anandamide did not induce capacitation process and a negative effect was obtained on sperm motility. The blockage of CB1-R by the specific antagonist SR141716 increased both capacitation and sperm motility suggesting an involvement of the CB1-R in the acquisition of sperm fertilizing activity. The evaluation of the triglycerides content, lipase and acyl-CoA dehydrogenase activities, suggest that anandamide exerts a lipogenetic effect on human sperm lipid metabolism. Concerning the glucose metabolism, anandamide increases GSK3 phosphorylation indicating that it is involved in the accumulation of energy substrates. G6PDH activity was not affected by anandamide. Interestingly, AEA is involved in insulin secretion by sperm. As insulin had been demonstrated to be an autocrine factor that triggers capacitation, the endocannabinoid might be inserted in the signaling cascade that induces this process. Altogether these findings highlight a pivotal involvement of the CB1-R in the control of sperm energy homeostasis and propose a new site of action for endocannabinoids in the control of energy metabolism.

Published
2009

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