The mammalian metabolite, 2-methoxyestradiol, affects p53 levels and apoptosis induction in transformed cells but not in normal cells

2-Methoxyestradiol: New perspectives in colon carcinoma treatment

“…Given that 2-ME might produce undesired effects on normal cells, we addressed this issue by analyzing cell proliferation of human FO46 normal fibroblasts after a 24 htreatment with 1 and 10 µM 2-ME and also after a further 24 h-recovery in drug-free medium. We did not observe a marked effect of 2-ME on cell viability (data not shown), in line with the original observation by Seegers et al (1997), who demonstrated that normal human skin fibroblasts are not affected by 2-ME. Accordingly, the comparison between normal human fibroblasts and melanoma cell lines revealed that the former cells were not sensitive to the treatment (Dobos et al 2004).…”

Superinduction of wild-type p53 protein after 2-methoxyestradiol treatment of Ad5p53-transduced cells induces tumor cell apoptosis

“…The apoptotic cells were labeled in situ with biotinylated dUTP in a reaction mixture employing exogenous TdT followed by¯uoresceinated avidin binding. H322, C, control untreated cell line (322-2ME), treated with 5 mM 2-MeOE 2 for 24 h; 322 dl312, cells transduced with 1 MOI empty adenoviral vectors for 24 h; 322-Ad-p53, cells infected with 1 MOI Ad5-p53 for 24 h; 322-Adp53-2ME, cells infected with 1 MOI Ad5-p53 (24 h) washed, and then treated with 5 mM 2-MeOE 2 for 24 h. After the appropriate treatments, all cells were grown in drug-free medium for 5 days and subjected to TdT-FACS analysis molecular basis for the preferential sensitivity of tumor cells is not understood, the 2-MeOE 2 e ect is speci®c to lung cancer cells when compared with normal bronchial epithelial cells (Seegers et al, 1997;Mukhopadhyay and Roth, 1997). 2-MeOE 2 alone can induce p53 in cancer cell lines containing endogenous wt p53, resulting in some degree of growth inhibition and apoptosis (Mukhopadhyay and Roth, 1997).…”

Inhibition of MDA-MB-231 cell cycle progression and cell proliferation by C-2-substituted oestradiolmono- andbis-3-O-sulphamates

“…3,4,37 However, the mechanism by which 2-MeOE2 and many other antimicrotubule agents couple mitotic arrest and cell death is poorly understood. It was previously shown that 2-MeOE2 induces apoptosis by increasing the phosphorylation of oncoproteins such as BCL-2.…”

“…2-MeOE2 induces apoptosis and inhibits angiogenesis in many tumour models, indicating that this compound has considerable potential as an antitumour agent. [1][2][3][4][5][6][7][8][9][10][11] Previous studies from our group have shown that these sulphamoylated derivatives induce an irreversible G2-M arrest and inhibit proliferation of not only androgen receptor 1ve/2ve prostrate, ovarian, and breast cancer cells, but also cells resistant to conventional chemotherapeutic agents, such as adriamycin and cisplatin. 26,27 In all these studies, sulphamoylated derivatives of 2-MeOE2, 2-MeOE2-MATE, and 2-MeOE2bisMATE are significantly more potent at inducing cell cycle arrest and apoptosis than 2-MeOE2.…”