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Apoptosis-related gene expression affected by a GnRH analogue without induction of programmed cell death in LNCaP cells.
Anticancer Res. 2004 Sep-Oct; 24(5A):2729-38.AR

Abstract

BACKGROUND

In this study we confirmed the ability of a Gonadotropin Releasing Hormone (GnRH) agonist, leuprorelin acetate (LA), to counteract or even suppress the 5alpha-dihydrotestosterone (DHT)-stimulated growth of androgen-sensitive prostate cancer cells (LNCaP). Since the cellular mechanisms mediating this effect are not well defined, we investigated the activity of LA, also in combination with DHT or with cyproterone acetate (CA), on the expression of genes (bcl-2, bax, c-myc) which may contribute to the proliferative behaviour of LNCaP cells. In addition, experiments aimed to evaluate the action of the analogue on apoptosis were performed.

MATERIALS AND METHODS

Gene expression was evaluated by RT-PCR and Western blotting on cells treated with LA (10(-11) or 10(-6) M), alone or combined with 10(-9) M DHT or 10(-7) M CA. The occurrence of apoptosis following treatment with LA (10(-11), 10(-6) or 10(-5) M), alone or combined with 10(-9) M DHT, was assessed by DNA fragmentation analysis.

RESULTS

Both the mRNA and protein of the anti-apoptotic gene bcl-2 were induced (30-125%) by DHT after 24-144 h. LA decreased bcl-2 mRNA (10-40%), while it did not unequivocally affect protein expression. The analogue always reduced (13-74%) both mRNA and protein levels obtained under DHT treatment. The mRNA and protein of the pro-apoptotic gene bax were down-regulated by DHT (15-40%), while LA generally induced bax protein but not its mRNA. LA counteracted DHT activity, even increasing bax protein levels over the controls. c-myc mRNA and protein were enhanced by DHT (15-45%) but down-regulated by LA (10-40%). Once more, the androgen effect was antagonized by LA, sometimes reducing c-myc content below the controls. CA produced the most similar effects to those triggered by DHT. The hormonal treatment did not induce any DNA fragmentation.

CONCLUSION

In spite of gene modulation, apoptosis was not observed under LA treatment, in agreement with the lack of a cell growth effect when the analogue was used alone. Nevertheless, the observed changes in gene expression may be directly or indirectly involved in the antiproliferative effect of LA on androgen-stimulated cells.

Authors+Show Affiliations

Institute of Histology and Embryology, Faculty of Medicine, Catholic University of the Sacred Heart, Largo F. Vito 1, 00168 Rome, Itaty.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15517879

Citation

Angelucci, Cristiana, et al. "Apoptosis-related Gene Expression Affected By a GnRH Analogue Without Induction of Programmed Cell Death in LNCaP Cells." Anticancer Research, vol. 24, no. 5A, 2004, pp. 2729-38.
Angelucci C, Iacopino F, Lama G, et al. Apoptosis-related gene expression affected by a GnRH analogue without induction of programmed cell death in LNCaP cells. Anticancer Res. 2004;24(5A):2729-38.
Angelucci, C., Iacopino, F., Lama, G., Capucci, S., Zelano, G., Boca, M., Pistilli, A., & Sica, G. (2004). Apoptosis-related gene expression affected by a GnRH analogue without induction of programmed cell death in LNCaP cells. Anticancer Research, 24(5A), 2729-38.
Angelucci C, et al. Apoptosis-related Gene Expression Affected By a GnRH Analogue Without Induction of Programmed Cell Death in LNCaP Cells. Anticancer Res. 2004 Sep-Oct;24(5A):2729-38. PubMed PMID: 15517879.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Apoptosis-related gene expression affected by a GnRH analogue without induction of programmed cell death in LNCaP cells. AU - Angelucci,Cristiana, AU - Iacopino,Fortunata, AU - Lama,Gina, AU - Capucci,Susanna, AU - Zelano,Giovanni, AU - Boca,Manila, AU - Pistilli,Alessandra, AU - Sica,Gigliola, PY - 2004/11/3/pubmed PY - 2004/12/16/medline PY - 2004/11/3/entrez SP - 2729 EP - 38 JF - Anticancer research JO - Anticancer Res VL - 24 IS - 5A N2 - BACKGROUND: In this study we confirmed the ability of a Gonadotropin Releasing Hormone (GnRH) agonist, leuprorelin acetate (LA), to counteract or even suppress the 5alpha-dihydrotestosterone (DHT)-stimulated growth of androgen-sensitive prostate cancer cells (LNCaP). Since the cellular mechanisms mediating this effect are not well defined, we investigated the activity of LA, also in combination with DHT or with cyproterone acetate (CA), on the expression of genes (bcl-2, bax, c-myc) which may contribute to the proliferative behaviour of LNCaP cells. In addition, experiments aimed to evaluate the action of the analogue on apoptosis were performed. MATERIALS AND METHODS: Gene expression was evaluated by RT-PCR and Western blotting on cells treated with LA (10(-11) or 10(-6) M), alone or combined with 10(-9) M DHT or 10(-7) M CA. The occurrence of apoptosis following treatment with LA (10(-11), 10(-6) or 10(-5) M), alone or combined with 10(-9) M DHT, was assessed by DNA fragmentation analysis. RESULTS: Both the mRNA and protein of the anti-apoptotic gene bcl-2 were induced (30-125%) by DHT after 24-144 h. LA decreased bcl-2 mRNA (10-40%), while it did not unequivocally affect protein expression. The analogue always reduced (13-74%) both mRNA and protein levels obtained under DHT treatment. The mRNA and protein of the pro-apoptotic gene bax were down-regulated by DHT (15-40%), while LA generally induced bax protein but not its mRNA. LA counteracted DHT activity, even increasing bax protein levels over the controls. c-myc mRNA and protein were enhanced by DHT (15-45%) but down-regulated by LA (10-40%). Once more, the androgen effect was antagonized by LA, sometimes reducing c-myc content below the controls. CA produced the most similar effects to those triggered by DHT. The hormonal treatment did not induce any DNA fragmentation. CONCLUSION: In spite of gene modulation, apoptosis was not observed under LA treatment, in agreement with the lack of a cell growth effect when the analogue was used alone. Nevertheless, the observed changes in gene expression may be directly or indirectly involved in the antiproliferative effect of LA on androgen-stimulated cells. SN - 0250-7005 UR - https://www.unboundmedicine.com/medline/citation/15517879/Apoptosis_related_gene_expression_affected_by_a_GnRH_analogue_without_induction_of_programmed_cell_death_in_LNCaP_cells_ L2 - http://ar.iiarjournals.org/cgi/pmidlookup?view=long&pmid=15517879 DB - PRIME DP - Unbound Medicine ER -