20.500.12556/RUL-148647 Cytotoxic effect of 13α-estrane derivatives on breast, endometrial and ovarian cancer cell lines 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. breast cancer endometrial cancer ovarian cancer estrane derivatives cytotoxicity novotvorbe dojk endometrijske novotvorbe novotvorbe jajčnikov derivati estrana citotoksičnost true false true Angleški jezik Slovenski jezik Članek v reviji 2023-08-28 14:02:42 2023-08-28 14:02:45 2023-08-30 03:11:44 0000-00-00 00:00:00 2023 0 0 7 str. art. 106350 Vol. 232 2023 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 616-006:577 1879-1220 10.1016/j.jsbmb.2023.106350 155861507 1-s2.0-S096007602300105X-main.pdf 1-s2.0-S096007602300105X-main.pdf 1 C7B9841434FAB01B958D48D7F8DF9C0D 772eac201068d90aef61eb1a741198dc6c969212111a1fbf92b4e03bdb532ce2 6d69f185-459b-11ee-a605-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=172932 https://www.sciencedirect.com/science/article/pii/S096007602300105X 0 cc4e1897-459a-11ee-a605-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=172931 Medicinska fakulteta 0 0 0