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      A lipid-modified estrogen derivative that treats breast cancer independent of estrogen receptor expression through simultaneous induction of autophagy and apoptosis

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          Abstract

          It is a challenge to develop a universal single drug that can treat breast cancer at single or multiple-stage complications, yet remains nontoxic to normal cells. The challenge is even greater when breast cancer-specific estrogen-based drugs are being developed which cannot act against multi-staged breast cancer complications owing to cells’ differential ER expression status and their possession of drug-resistant and metastatic phenotypes. We report here the development of a first cationic lipid-conjugated estrogenic derivative (ESC8) that kills breast cancer cells independent of their estrogen receptor (ER) expression status. This ESC8 molecule apparently is nontoxic to normal breast epithelial cells, as well as to other non-cancer cells. ESC8 induces apoptosis through an intrinsic pathway in ER-negative MDA-MB-231 cells. In addition, ESC8-treatment induces autophagy in these cells by interfering with the mTOR activity. This is the first example of an estrogen structure-based molecule that co-induces apoptosis and autophagy in breast cancer cells. Further in vivo study confirms the role of this molecule in tumor regression. Together, our results open new perspective of breast cancer chemotherapy through a single agent, which could provide the therapeutic benefit across all stages of breast cancer.

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          Author and article information

          Journal
          101150042
          30118
          Mol Cancer Res
          Mol. Cancer Res.
          Molecular cancer research : MCR
          1541-7786
          1557-3125
          27 June 2017
          02 February 2011
          March 2011
          23 August 2017
          : 9
          : 3
          : 364-374
          Affiliations
          [+ ]Department of Biochemistry & Molecular Biology, Mayo Clinic, Rochester, MN, USA
          []Division of Lipid Science & Technology, Indian Institute of Chemical Technology, Hyderabad, Andhra Pradesh, India
          []School of Life Sciences, University of Hyderabad, Hyderabad, Andhra Pradesh, India
          []Division of Pharmaceutics and Drug Standardization, Central Drug Research Institute, Lucknow, Uttar Pradesh 226 001, India
          Author notes
          Corresponding authors: Debabrata Mukhopadhyay, Department of Biochemistry & Molecular Biology, Mayo Clinic, Guggenheim 1321, 200 First St. S.W., Rochester, MN 55905. mukhopadhyay.debabrata@ 123456mayo.edu and Rajkumar Banerjee, Room No. 345, Division of Lipid Science & Technology, Indian Institute of Chemical Technology, Hyderabad, Andhra Pradesh 500 007 India. banerjee@ 123456iict.res.in
          [#]

          These authors contributed equally

          Article
          PMC5568550 PMC5568550 5568550 nihpa881953
          10.1158/1541-7786.MCR-10-0526
          5568550
          21289296
          6cfd2118-dd18-47be-9f45-04635c575d64
          History
          Categories
          Article

          Breast cancer,ESC8,Apoptosis,Autophagy,Mice model
          Breast cancer, ESC8, Apoptosis, Autophagy, Mice model

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