Hormone receptor binding, selectivity and cytotoxicity of steroid D-homo lactone loaded chitosan nanoparticles for the treatment of breast and prostate cancer cells
Authorized Users Only
2022
Authors
Kuzminac, Ivana
Ćelić, Andjelka S.
Bekić, Sofija S.
Kojić, Vesna

Savić, Marina P.
Ignjatović, Nenad

Article (Accepted Version)
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Show full item recordAbstract
Chemically modified steroids have a long history as anti-neoplastic drugs. Incorporation of a lactone moiety in the steroid nucleus, as in previously obtained 3β-acetoxy-17-oxa-17a-homoandrost-5-en-16-one (A) and 3β-hidroxy-17-oxa-17a-homoandrost-5-en-16-one (B), often results in enhanced anticancer properties. In this work, chitosan-based (Ch) nanoparticles were created and loaded with potent anticancer steroidal compounds, A and B. Changes to hormone receptor binding and cytotoxicity were then measured. In agreement with our previous results for A and B, A- and B-loaded Ch displayed cytotoxic properties against cancer cell lines. Both A-Ch and B-Ch showed activity toward estrogen negative breast cancer (MDA-MB-231) and androgen negative prostate cancer cell lines (PC-3). Greater selectivity toward cancer cells versus healthy lung fibroblast (MRC-5) was observed for B-Ch particles. Cell viability and cytotoxicity measurements after a recovery period indicate more robust recovery of he...althy cells versus malignant cells. Compounds A and B or their Ch-encapsulated forms were shown to have negligible affinity for the ligand binding domain of estrogen receptor β or the androgen receptor in a fluorescent yeast screen, suggesting a lack of estrogenicity and androgenicity. Steroid-loaded chitosan nanoparticles display strong cytotoxicity towards MDA-MB-231 and PC-3 with a lack of hormone activity, indicating their safety and efficacy.
Keywords:
androstane / D-homo lactone / nanocarriers / estrogen / androgen receptors / cancerSource:
Colloids and Surfaces B: Biointerfaces, 2022, 216, 112597-Publisher:
- Elsevier BV
Funding / projects:
- Ministry of Education, Science and Technological Development, Republic of Serbia, Grant no. 200175 (Institute of Technical Sciences of SASA, Belgrade) (RS-200175)
- Provincial Secretariat for Higher Education and Scientific Research of the Autonomous Province of Vojvodina, Project: New steroid derivatives - potential chemotherapeutics, No. 142–451-2667/2021
- COST Action CA 17140 “Cancer Nanomedicine from the Bench to the Bedside”
Note:
- This is the peer-reviewed manuscript of the article: Kuzminac, Ivana Z., Ćelić, Andjelka S., Bekić, Sofija S., Kojić, Vesna, Savić, Marina P., Ignjatović, Nenad, "Hormone receptor binding, selectivity and cytotoxicity of steroid D-homo lactone loaded chitosan nanoparticles for the treatment of breast and prostate cancer cells" in Colloids and Surfaces B: Biointerfaces, 216 (2022-08):112597, https://doi.org/10.1016/j.colsurfb.2022.112597
Related info:
DOI: 10.1016/j.colsurfb.2022.112597
ISSN: 0927-7765
WoS: 00080799480000
Scopus: 2-s2.0-85131462166
Institution/Community
Институт техничких наука САНУ / Institute of Technical Sciences of SASATY - JOUR AU - Kuzminac, Ivana AU - Ćelić, Andjelka S. AU - Bekić, Sofija S. AU - Kojić, Vesna AU - Savić, Marina P. AU - Ignjatović, Nenad PY - 2022 UR - https://dais.sanu.ac.rs/123456789/13031 AB - Chemically modified steroids have a long history as anti-neoplastic drugs. Incorporation of a lactone moiety in the steroid nucleus, as in previously obtained 3β-acetoxy-17-oxa-17a-homoandrost-5-en-16-one (A) and 3β-hidroxy-17-oxa-17a-homoandrost-5-en-16-one (B), often results in enhanced anticancer properties. In this work, chitosan-based (Ch) nanoparticles were created and loaded with potent anticancer steroidal compounds, A and B. Changes to hormone receptor binding and cytotoxicity were then measured. In agreement with our previous results for A and B, A- and B-loaded Ch displayed cytotoxic properties against cancer cell lines. Both A-Ch and B-Ch showed activity toward estrogen negative breast cancer (MDA-MB-231) and androgen negative prostate cancer cell lines (PC-3). Greater selectivity toward cancer cells versus healthy lung fibroblast (MRC-5) was observed for B-Ch particles. Cell viability and cytotoxicity measurements after a recovery period indicate more robust recovery of healthy cells versus malignant cells. Compounds A and B or their Ch-encapsulated forms were shown to have negligible affinity for the ligand binding domain of estrogen receptor β or the androgen receptor in a fluorescent yeast screen, suggesting a lack of estrogenicity and androgenicity. Steroid-loaded chitosan nanoparticles display strong cytotoxicity towards MDA-MB-231 and PC-3 with a lack of hormone activity, indicating their safety and efficacy. PB - Elsevier BV T2 - Colloids and Surfaces B: Biointerfaces T1 - Hormone receptor binding, selectivity and cytotoxicity of steroid D-homo lactone loaded chitosan nanoparticles for the treatment of breast and prostate cancer cells SP - 112597 VL - 216 DO - 10.1016/j.colsurfb.2022.112597 UR - https://hdl.handle.net/21.15107/rcub_dais_13031 ER -
@article{ author = "Kuzminac, Ivana and Ćelić, Andjelka S. and Bekić, Sofija S. and Kojić, Vesna and Savić, Marina P. and Ignjatović, Nenad", year = "2022", abstract = "Chemically modified steroids have a long history as anti-neoplastic drugs. Incorporation of a lactone moiety in the steroid nucleus, as in previously obtained 3β-acetoxy-17-oxa-17a-homoandrost-5-en-16-one (A) and 3β-hidroxy-17-oxa-17a-homoandrost-5-en-16-one (B), often results in enhanced anticancer properties. In this work, chitosan-based (Ch) nanoparticles were created and loaded with potent anticancer steroidal compounds, A and B. Changes to hormone receptor binding and cytotoxicity were then measured. In agreement with our previous results for A and B, A- and B-loaded Ch displayed cytotoxic properties against cancer cell lines. Both A-Ch and B-Ch showed activity toward estrogen negative breast cancer (MDA-MB-231) and androgen negative prostate cancer cell lines (PC-3). Greater selectivity toward cancer cells versus healthy lung fibroblast (MRC-5) was observed for B-Ch particles. Cell viability and cytotoxicity measurements after a recovery period indicate more robust recovery of healthy cells versus malignant cells. Compounds A and B or their Ch-encapsulated forms were shown to have negligible affinity for the ligand binding domain of estrogen receptor β or the androgen receptor in a fluorescent yeast screen, suggesting a lack of estrogenicity and androgenicity. Steroid-loaded chitosan nanoparticles display strong cytotoxicity towards MDA-MB-231 and PC-3 with a lack of hormone activity, indicating their safety and efficacy.", publisher = "Elsevier BV", journal = "Colloids and Surfaces B: Biointerfaces", title = "Hormone receptor binding, selectivity and cytotoxicity of steroid D-homo lactone loaded chitosan nanoparticles for the treatment of breast and prostate cancer cells", pages = "112597", volume = "216", doi = "10.1016/j.colsurfb.2022.112597", url = "https://hdl.handle.net/21.15107/rcub_dais_13031" }
Kuzminac, I., Ćelić, A. S., Bekić, S. S., Kojić, V., Savić, M. P.,& Ignjatović, N.. (2022). Hormone receptor binding, selectivity and cytotoxicity of steroid D-homo lactone loaded chitosan nanoparticles for the treatment of breast and prostate cancer cells. in Colloids and Surfaces B: Biointerfaces Elsevier BV., 216, 112597. https://doi.org/10.1016/j.colsurfb.2022.112597 https://hdl.handle.net/21.15107/rcub_dais_13031
Kuzminac I, Ćelić AS, Bekić SS, Kojić V, Savić MP, Ignjatović N. Hormone receptor binding, selectivity and cytotoxicity of steroid D-homo lactone loaded chitosan nanoparticles for the treatment of breast and prostate cancer cells. in Colloids and Surfaces B: Biointerfaces. 2022;216:112597. doi:10.1016/j.colsurfb.2022.112597 https://hdl.handle.net/21.15107/rcub_dais_13031 .
Kuzminac, Ivana, Ćelić, Andjelka S., Bekić, Sofija S., Kojić, Vesna, Savić, Marina P., Ignjatović, Nenad, "Hormone receptor binding, selectivity and cytotoxicity of steroid D-homo lactone loaded chitosan nanoparticles for the treatment of breast and prostate cancer cells" in Colloids and Surfaces B: Biointerfaces, 216 (2022):112597, https://doi.org/10.1016/j.colsurfb.2022.112597 ., https://hdl.handle.net/21.15107/rcub_dais_13031 .