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

Sutapa Sinha, Sayantani Roy, Bathula Surendar Reddy, Krishnendu Pal, Godeshala Sudhakar, Seethalakshmi Iyer, Shamit Dutta, Enfeng Wang, Pawan Kumar Vohra, Karnati Rammohan Roy, Pallu Reddanna, Debabrata Mukhopadhyay, Rajkumar Banerjee

Research output: Contribution to journalArticle

26 Scopus citations

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 that cannot act against multistaged breast cancer complications owing to the cells differential estrogen receptor (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 ER expression status. This ESC8 molecule apparently is nontoxic to normal breast epithelial cells, as well as to other noncancer 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 coinduces 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.

Original languageEnglish (US)
Pages (from-to)364-374
Number of pages11
JournalMolecular Cancer Research
Volume9
Issue number3
DOIs
StatePublished - Mar 2011

ASJC Scopus subject areas

  • Molecular Biology
  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'A lipid-modified estrogen derivative that treats breast cancer independent of estrogen receptor expression through simultaneous induction of autophagy and apoptosis'. Together they form a unique fingerprint.

Cite this