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2-Methoxyestradiol induces mitochondria dependent apoptotic signaling in pancreatic cancer cells

Oncogene volume 21, pages 4149–4157 (2002)Cite this article

Abstract

The antiproliferative action of 2-methoxyestradiol (2-ME), an endogenous estrogen metabolite is specific for cancer cells and is mediated by the induction of programmed cell death or apoptosis. But the identity of the downstream effectors of apoptotic signaling induced by 2-ME is not known. In the present study, we explored the effect of 2-ME on apoptosis in a panel of human pancreatic cancer cell lines. We have identified two categories of pancreatic cancer cell lines, which are either sensitive to 2-ME such as MIA PaCa-2, CFPAC-1, PANC-1, or non-sensitive to 2-ME such as Hs 766T. The results presented here indicated that the cell lines responsive to 2-ME could undergo apoptosis either by G2-M arrest (PANC-1) with Bcl-xL phosphorylation or by the accumulation of tetraploid cells in G1-S region (MIA PaCa-2) without Bcl-2/ Bcl-xL phosphorylation. Furthermore, 2-ME induced apoptosis in pancreatic cancer cells is mitochondria dependent as evident by the release of cytochrome c into the cytosol. 2-ME exposed cells exhibit Bid cleavage that is accompanied by the translocation of Bax into the mitochondria. Also 2-ME could induce phosphorylation of Bcl-xL in G2-M arrested cells, thus indicating the involvement of various anti- and pro-apoptotic regulators in the signaling cascade. The dissection of differential response of pancreatic cancer cell lines holds promise for future therapeutic intervention.

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Acknowledgements

We thank Michael Sramkoski for FACS analysis and Kay Haas for technical assistance. The work was supported by National Cancer Institute Grant CA77328.

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Authors and Affiliations

  1. Department of Research, Pharmacology, Ireland Cancer Center, MetroHealth Medical Center, Case Western Reserve University, Cleveland, 44109, Ohio, OH, USA

    Suparna Qanungo, Aruna Basu, Madhusudan Das & Subrata Haldar

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  1. Suparna Qanungo
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  2. Aruna Basu
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Correspondence to Subrata Haldar.

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Qanungo, S., Basu, A., Das, M. et al. 2-Methoxyestradiol induces mitochondria dependent apoptotic signaling in pancreatic cancer cells. Oncogene 21, 4149–4157 (2002). https://doi.org/10.1038/sj.onc.1205508

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