In vitro effects of 2‐methoxyestradiol on cell morphology and Cdc2 Kinase activity in SNO oesophageal carcinoma cells

Abstract

The effects of 1 x 10 -6 M exogenous 2-methoxyestradiol (2 ME) were determined on cell morphology and cell division cycle (Cdc) 2 kinase activity in SNO oesophageal carcinoma cells. Mitotic indices revealed an increase in metaphase cells (11.2%) when compared to the 0.5% vehicle-treated cells after 18 h of exposure to 2 ME. Vehicletreated control cells did not show any hallmarks of apoptosis after 18 h of exposure to dimethyl sulphoxide. Only 0.5% of 2 ME-treated cells showed characteristics of apoptosis. Conversely, increased morphological hallmarks of apoptosis were observed in SNO-treated cells after 21.5 h of 2 ME exposure. When compared to the 0.5% in vehicle-treated cells, 4.7% of cells were in apoptosis. Furthermore, 34.1% of cells were blocked in metaphase after 21.5 h of 2 ME exposure compared to 0.6% of vehicle-control cells. In addition, Cdc2 kinase activity was statistically significantly increased (1.3-fold) (p < 0.005) in 2 ME-treated cells when compared to vehicle-treated controls. The present preliminary study suggests that the accumulation observed in metaphase cells and the increase in Cdc2 kinase activity caused by 2 ME are consistent with morphological hallmarks of mitotic arrest and disrupted mitotic spindle formation, thus leading to induction of apoptosis in SNO cells.

Docking, Synthesis, and in vitro Evaluation of Antimitotic Estrone Analogs

“…The GI 50 concentrations for the compounds are summarized in Table 1 . In in vitro studies conducted in our laboratory, 2‐ME showed an antiproliferative effect on HeLa, SNO, MCF‐7, and MCF‐12A cells in a concentration range of 1–2μ m (43–45). Accordingly, Edsall et al.…”

Role of 2-methoxyestradiol, an Endogenous Estrogen Metabolite, in Health and Disease

“…For example, 2ME 2 activates JNK kinases in prostate cancer cells [59], Ewing sarcoma cells [60,61] and nasopharyngeal carcinoma cells [62] to induce cell death by mitochondrial-dependent apoptotic pathways and/or autophagy. Furthermore, 2ME 2 activates a RNA-dependent protein kinase (PKR) [63] to induce autophagy in osteosarcoma cells and induces apoptosis in esophageal carcinoma cells by increasing cdc2 kinase activity [64].…”

Dietary intake of lignans and risk of adenocarcinoma of the esophagus and gastroesophageal junction

“…Some potential mechanisms that might be involved in such an association are available. The presence of estrogen receptors in esophageal tissue has been identified, and in vitro studies indicate that estrogens might inhibit esophageal carcinogenesis [15][16][17]. Metabolites of lignans might lead to in vivo and vitro activation of estrogen receptor-mediated events [6].…”