The oestrogen metabolite 2-methoxyoestradiol alone or in combination with tumour necrosis factor-related apoptosis-inducing ligand mediates apoptosis in cancerous but not healthy cells of the human endometrium

Abstract

The oestrogen metabolite 2-methoxyoestradiol alone or in combination with tumour necrosis factor-related apoptosis-inducing ligand mediates apoptosis in cancerous but not healthy cells of the human endometrium AbstractCancers of the reproductive tract account for 12% of all malignancies in women. As previous studies have shown that oestrogen metabolites can cause apoptosis, we characterised the effect of oestrogen and oestrogen metabolites on non-cancerous and cancerous human endometrial cells. Herein, we demonstrate that 2-methoxyoestradiol (2ME), but not 17b-oestradiol, induces apoptosis in cancer cell lines and primary cultured tumours of endometrial origin. In contrast, 2ME had no effect on cell viability of corresponding normal tissue. This ability of 2ME to induce apoptosis does not require oestrogen receptor activation, but is associated with increased entry into the G2/M phases of the cell cycle and the activation of both the intrinsic and the extrinsic apoptotic pathways. The selective behaviour of 2ME on cancerous as opposed to normal tissue may be due to a reduction in 17b-hydroxysteroid dehydrogenase type II levels in cancer cells and to a differential down-regulation of superoxide dismutase. Furthermore, we demonstrate that pre-treatment with 2ME enhances the sensitivity of reproductive tract cancer cells to the apoptotic drug tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), without the loss in cell viability to normal cells incurred by currently chemotherapeutic drugs. In conclusion, 2ME, alone or in combination with TRAIL, may be an effective treatment for cancers of uterine origin with minimal toxicity to corresponding healthy female reproductive tissue.

Metformin, at Concentrations Corresponding to the Treatment of Diabetes, Potentiates the Cytotoxic Effects of Carboplatin in Cultures of Ovarian Cancer Cells

“…25,26 Previous publications from our laboratory have demonstrated that the loss of cell viability in this assay corresponds to ovarian cancer cell apoptosis. 20,21 Figures 2 and 3 demonstrate that the reduction in cell viability with chemotherapies tested in A2780 and SKOV3 is enhanced when cells were preexposed to metformin for 24 hours. Unsurprisingly, given that the 3 chemotherapies used have differing modes of action and that every cancer (and cell line) is unique, there were differing responses to each combination of metformin.…”

“…20,21 The cells were seeded at 50% density. Each experiment was repeated at least 3 times with 5 replicates per experiment.…”

Red Maca (Lepidium meyenii) did not affect cell viability despite increased androgen receptor and prostate-specific antigen gene expression in the human prostate cancer cell line LNCaP

“…Therefore, it is probable that red Maca could be used as a source for active principles against a wide range of male pathologies. In LNCaP cells, we also explored whether red Maca extract is able to potentiate apoptotic activity induced by two anticancer drugs Taxol and 2-methoxyestradiol (2ME) (Kato et al, 2007;Parada-Bustamante et al, 2015). In LNCaP cells, we also explored whether red Maca extract is able to potentiate apoptotic activity induced by two anticancer drugs Taxol and 2-methoxyestradiol (2ME) (Kato et al, 2007;Parada-Bustamante et al, 2015).…”

Hyperthermia Promotes Apoptosis and Suppresses Invasion in C6 Rat Glioma Cells

“…TRAIL is well known to play a critical role as an inducer of apoptosis in a variety of cancer cells in vitro and has been shown to limit tumor growth efficiently in vivo, with minimal damage to normal tissues (Lee et al, 1993;Ashkenazi et al, 1999;Walczak et al, 1999;Kato et al, 2007;Yoo and Lee, 2008). TRAIL is expressed as a type II integral membrane protein belonging to the tumor necrosis factor (TNF) superfamily (Lee et al, 1993;Ashkenazi et al, 1999;Walczak et al, 1999;Kato et al, 2007;Yoo and Lee, 2008).…”