Antiproliferative effect of normal and 13-epi-d-homoestrone and their 3-methyl ethers on human reproductive cancer cell lines

Antiproliferative and antimetastatic properties of D-ring modified estrogen analogs on cervical cancer cell lines

“…After incubation for 24 h both of the sensitive cell lines (HeLa and C-33 A) showed a significant elevation of cell number in the G2/M phase, indicating a cell cycle blockade at G2/M. These results are similar to those previously reported on other steroid analogs such as the natural steroid alkaloid solanidine, the natural estrogen metabolite 2-ME or the synthetic D-homoestrone [12,55,57]. For a precise distinction between the G2 and M phases, phosphorylated histone-H3 (Ser10) was measured after D-SET treatment.…”

“…A large body of evidence indicates that steroid-like triterpenes, e.g. betulinic or oleanolic acid and their derivatives exert potent proapoptotic and antimigratory effects on numerous human cancer cell lines [52][53][54][55][56][57][58] . Antiproliferative effects of several other natural steroids have been described: steroid alkaloids from the Solanaceae family; solasonine, solamargine, solanine, or some marine sponge extracts;…”

“…The conventional receptorbinding and activating capacity is an intriguing question of compounds with steroid structure in their expected therapeutic use. It has been described that D-homoestrone, does not exert estrogenic effect in an in vivo uterotrophic assay system [57]. A review of the literature, revealed data about a negative association between the opened D-ring and the estrogen receptor (ER)-binding capacity.…”

“…Our previous studies demonstrated that D-ring modification in the estrogen structure can cause a potent antiproliferative effect in vitro [20,32,57,60]; we also reported about the considerable antitumor effects of several D-secoestrone derivatives in eight different reproductive cancer cell lines [32]. Among these analogs, a compound with a 3-triazole substituent (D-SET) was found to the most effective on cervical carcinoma cell lines, while it has no significant inhibitory effect on the non-cancerous human fetal lung fibroblast (MRC-5) cells.…”

Characterization of antiproliferative activities of triazolyl-steroid derivatives

“…Non-toxic concentrations of digitoxin and digoxin inhibit growth and induce apoptosis in different human malignant cell lines, whereas highly proliferating normal cells are not affected. Although these compounds have no use as anticancer agents because of the cardiac side effects, the structure of these compounds can be used for the development of novel anticancer agents (Mijatovic and Kiss, 2013 (Minorics et al, 2012, Berényi et al, 2013, Kovács et al, 2014, Mernyák et al, 2014 et al, 1986, Alvarez et al, 1994, Genin et al, 2000, Zhou and Wang, 2012, Sahu et al, 2013. The introduction of a triazole ring at position 3 of the natural triterpene betulinic acid resulted in a set of compounds with considerable antiproliferative potency and proapoptotic capacity (Majeed et al, 2013).…”