Effects of Dibutylphthalate and Steroid Hormone Mixture on Human Prostate Cells
Phthalates are a family of aromatic chemical compounds mainly used as plasticizers. Among phthalates, di-n-butyl phthalate (DBP) is a low-molecular-weight phthalate used as a component of many cosmetic products, such as nail polish, and other perfumed personal care products. DBP has toxic effects on...
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| Format: | Article |
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MDPI AG
2023-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/18/14341 |
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| author | Aldo Mileo Teresa Chianese Gianluca Fasciolo Paola Venditti Anna Capaldo Luigi Rosati Maria De Falco |
| author_facet | Aldo Mileo Teresa Chianese Gianluca Fasciolo Paola Venditti Anna Capaldo Luigi Rosati Maria De Falco |
| author_sort | Aldo Mileo |
| collection | DOAJ |
| description | Phthalates are a family of aromatic chemical compounds mainly used as plasticizers. Among phthalates, di-n-butyl phthalate (DBP) is a low-molecular-weight phthalate used as a component of many cosmetic products, such as nail polish, and other perfumed personal care products. DBP has toxic effects on reproductive health, inducing testicular damage and developmental malformations. Inside the male reproductive system, the prostate gland reacts to both male and female sex steroids. For this reason, it represents an important target of endocrine-disrupting chemicals (EDCs), compounds that are able to affect the estrogen and androgen signaling pathways, thus interfering with prostate homeostasis and inducing several prostate pathologies. The aim of this project was to investigate the effects of DBP, alone and in combination with testosterone (T), 17β-estradiol (E2), and both, on the normal PNT1A human prostate cell-derived cell line, to mimic environmental contamination. We showed that DBP and all of the tested mixtures increase cell viability through activation of both estrogen receptor α (ERα) and androgen receptor (AR). DBP modulated steroid receptor levels in a nonmonotonic way, and differently to endogenous hormones. In addition, DBP translocated ERα to the nucleus over different durations and for a more prolonged time than E2, altering the normal responsiveness of prostate cells. However, DBP alone seemed not to influence AR localization, but AR was continuously and persistently activated when DBP was used in combination. Our results show that DBP alone, and in mixture, alters redox homeostasis in prostate cells, leading to a greater increase in cell oxidative susceptibility. In addition, we also demonstrate that DBP increases the migratory potential of PNT1A cells. In conclusion, our findings demonstrate that DBP, alone and in mixtures with endogenous steroid hormones, acts as an EDC, resulting in an altered prostate cell physiology and making these cells more prone to cancer transformation. |
| first_indexed | 2024-03-10T22:38:45Z |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T22:38:45Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-01189d8f7b614cfbaa4894bae5fa1d0a2023-11-19T11:11:19ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-09-0124181434110.3390/ijms241814341Effects of Dibutylphthalate and Steroid Hormone Mixture on Human Prostate CellsAldo Mileo0Teresa Chianese1Gianluca Fasciolo2Paola Venditti3Anna Capaldo4Luigi Rosati5Maria De Falco6Department of Biology, University Federico II of Naples, Via Cinthia 26, 80126 Naples, ItalyDepartment of Biology, University Federico II of Naples, Via Cinthia 26, 80126 Naples, ItalyDepartment of Biology, University Federico II of Naples, Via Cinthia 26, 80126 Naples, ItalyDepartment of Biology, University Federico II of Naples, Via Cinthia 26, 80126 Naples, ItalyDepartment of Biology, University Federico II of Naples, Via Cinthia 26, 80126 Naples, ItalyDepartment of Biology, University Federico II of Naples, Via Cinthia 26, 80126 Naples, ItalyDepartment of Biology, University Federico II of Naples, Via Cinthia 26, 80126 Naples, ItalyPhthalates are a family of aromatic chemical compounds mainly used as plasticizers. Among phthalates, di-n-butyl phthalate (DBP) is a low-molecular-weight phthalate used as a component of many cosmetic products, such as nail polish, and other perfumed personal care products. DBP has toxic effects on reproductive health, inducing testicular damage and developmental malformations. Inside the male reproductive system, the prostate gland reacts to both male and female sex steroids. For this reason, it represents an important target of endocrine-disrupting chemicals (EDCs), compounds that are able to affect the estrogen and androgen signaling pathways, thus interfering with prostate homeostasis and inducing several prostate pathologies. The aim of this project was to investigate the effects of DBP, alone and in combination with testosterone (T), 17β-estradiol (E2), and both, on the normal PNT1A human prostate cell-derived cell line, to mimic environmental contamination. We showed that DBP and all of the tested mixtures increase cell viability through activation of both estrogen receptor α (ERα) and androgen receptor (AR). DBP modulated steroid receptor levels in a nonmonotonic way, and differently to endogenous hormones. In addition, DBP translocated ERα to the nucleus over different durations and for a more prolonged time than E2, altering the normal responsiveness of prostate cells. However, DBP alone seemed not to influence AR localization, but AR was continuously and persistently activated when DBP was used in combination. Our results show that DBP alone, and in mixture, alters redox homeostasis in prostate cells, leading to a greater increase in cell oxidative susceptibility. In addition, we also demonstrate that DBP increases the migratory potential of PNT1A cells. In conclusion, our findings demonstrate that DBP, alone and in mixtures with endogenous steroid hormones, acts as an EDC, resulting in an altered prostate cell physiology and making these cells more prone to cancer transformation.https://www.mdpi.com/1422-0067/24/18/14341phthalatesdi-n-butyl phthalate (DBP)endocrine-disrupting chemicals (EDCs)prostate glandsteroid receptorsestrogens |
| spellingShingle | Aldo Mileo Teresa Chianese Gianluca Fasciolo Paola Venditti Anna Capaldo Luigi Rosati Maria De Falco Effects of Dibutylphthalate and Steroid Hormone Mixture on Human Prostate Cells International Journal of Molecular Sciences phthalates di-n-butyl phthalate (DBP) endocrine-disrupting chemicals (EDCs) prostate gland steroid receptors estrogens |
| title | Effects of Dibutylphthalate and Steroid Hormone Mixture on Human Prostate Cells |
| title_full | Effects of Dibutylphthalate and Steroid Hormone Mixture on Human Prostate Cells |
| title_fullStr | Effects of Dibutylphthalate and Steroid Hormone Mixture on Human Prostate Cells |
| title_full_unstemmed | Effects of Dibutylphthalate and Steroid Hormone Mixture on Human Prostate Cells |
| title_short | Effects of Dibutylphthalate and Steroid Hormone Mixture on Human Prostate Cells |
| title_sort | effects of dibutylphthalate and steroid hormone mixture on human prostate cells |
| topic | phthalates di-n-butyl phthalate (DBP) endocrine-disrupting chemicals (EDCs) prostate gland steroid receptors estrogens |
| url | https://www.mdpi.com/1422-0067/24/18/14341 |
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