The induction of apoptosis by a newly synthesized diosgenyl saponin through the suppression of estrogen receptor-α in MCF-7 human breast cancer cells

Jaemoo Chun, Lina Han, Mei Ying Xu, Bo Wang, Mao Sheng Cheng, Yeong Shik Kim

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Estrogen receptor (ER)-α is an important therapeutic target in the clinical treatment of breast cancer. A potential down-regulator of ER-α, diosgenyl α-l-rhamnopyranosyl-(1→2)-[β-d-xylopyranosyl-(1→4)]-α-l-arabinopyranoside is a newly synthesized diosgenyl saponin named compound 22. This study evaluated the in vitro mechanism of compound 22 as an anticancer agent for breast cancer. Our results indicated that compound 22 selectively inhibited proliferation and induced apoptosis in ER-positive MCF-7 cells, compared with ER-negative MDA-MB-231 and MCF-10A cells. Western blot analysis showed that compound 22 decreased the expression of procaspase-3, procaspase-8, and survivin; and increased the expression of Fas ligand and cleaved PARP1 in MCF-7 cells, indicating that compound 22-induced apoptosis was mediated by the extrinsic pathway. This apoptosis was associated with the suppression of ER-α protein and mRNA expression and the inhibition of ER-DNA binding to the estrogen responsive element. Moreover, ER-α mediated gene expression such as c-Myc and cyclin D1 was reduced, and the activation of p38 and ERK 1/2 was significantly decreased after treatment with compound 22 in MCF-7 cells. Taken together, these results demonstrate that compound 22 down-regulates ER-α expression and induces apoptosis through the extrinsic pathway, suggesting that compound 22 may be effective in the treatment of ER-positive breast cancer.

Original languageEnglish (US)
Pages (from-to)1477-1486
Number of pages10
JournalArchives of Pharmacal Research
Volume37
Issue number11
DOIs
StatePublished - Nov 2014

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery
  • Organic Chemistry

Fingerprint Dive into the research topics of 'The induction of apoptosis by a newly synthesized diosgenyl saponin through the suppression of estrogen receptor-α in MCF-7 human breast cancer cells'. Together they form a unique fingerprint.

Cite this