Cytotoxic effect of 13α-estrane derivatives on breast, endometrial and ovarian cancer cell lines

Zottel, Alja (author), Jójárt, Rebeka (author), Ágoston, Henrietta (author), Hafner, Eva (author), Lipušček, Neža (author), Mernyák, Erzsébet (author), Lanišnik-Rižner, Tea (author)

Hormone-dependent cancers such as breast, uterine, and ovarian cancers account for more than 35% of all cancers in women. Worldwide, these cancers occur in more than 2.7 million women/year and account for 22% of cancer-related deaths/year. The generally accepted mechanism for the pathophysiology of estrogen-dependent cancers is estrogen receptor-mediated cell proliferation associated with an increased number of mutations. Therefore, drugs that can interfere with either local estrogen formation or estrogen action via estrogen receptors are needed. Estrane derivatives that have low or minimal estrogenic activity can affect both pathways. In this study, we investigated the effect of 36 different estrane derivatives on the proliferation of eight breast, endometrial, and ovarian cancer cell lines and the corresponding three control cell lines. Estrane derivatives 3 and 4_2Cl showed a stronger effect on the endometrial cancer cell lines KLE and Ishikawa, respectively, compared with the control cell line HIEEC, with IC50 values of 32.6 microM and 17.9 microM, respectively. Estrane derivative 4_2Cl was most active in the ovarian cancer cell line COV362 compared to the control cell line HIO80 with an IC50 value of 3.6 microM. In addition, estrane derivative 2_4I showed a strong antiproliferative effect on endometrial and ovarian cancer cell lines, while the effect on the control cell line was slight or absent. The addition of halogen at carbon 2 and/or 4 in estrane derivatives 1 and 2 increased the selectivity for endometrial cancer cells. Overall, these results suggest that single estrane derivatives are efficient cytotoxic agents for endometrial and ovarian cancer cell lines, and thus potential lead compounds for drug development.

• Language: English
• Keywords: breast cancer, endometrial cancer, ovarian cancer, estrane derivatives, cytotoxicity
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2023
• Number of pages: 7 str.
• Numbering: Vol. 232, art. 106350
• PID: 20.500.12556/RUL-148647
• UDC: 616-006:577
• ISSN on article: 1879-1220
• DOI: 10.1016/j.jsbmb.2023.106350
• COBISS.SI-ID: 155861507
• Publication date in RUL: 28.08.2023

Record is a part of a journal

• Title: The journal of steroid biochemistry and molecular biology
• Shortened title: J. steroid biochem. mol. biol.
• Publisher: Elsevier
• ISSN: 1879-1220
• COBISS.SI-ID: 57401603

Licences

• License: CC BY-NC-ND 4.0, Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
• Link: http://creativecommons.org/licenses/by-nc-nd/4.0/
• Description: The most restrictive Creative Commons license. This only allows people to download and share the work for no commercial gain and for no other purposes.

Secondary language

• Language: Slovenian
• Keywords: novotvorbe dojk, endometrijske novotvorbe, novotvorbe jajčnikov, derivati estrana, citotoksičnost