Synthesis of Breast Cancer Targeting Conjugate of Temporin-SHa Analog and its Effect on Pro- and Anti-Apoptotic Protein Expression in MCF-7 Cells

Farzana Shaheen, Muhammad Nadeem-ul-Haque, Aqeel Ahmed, Shabana U. Simjee, A. Ganesan, Almas Jabeen, Zafar Ali Shah, M. Iqbal Choudhary

Research output: Contribution to journalArticle

4 Citations (Scopus)
15 Downloads (Pure)

Abstract

The frog natural product temporin-SHa (FLSGIVGMLGKLFamide) is a potent antimicrobial peptide, as is the analog [S3K]SHa. By solid-phase synthesis, we prepared temporin-SHa and several temporin-SHa analogs with one or more D-alanine residues incorporated. The natural product and the analog [G10a]SHa were found to be cytotoxic in mammalian cell lines and induce cell death. To achieve selectivity, we conjugated the analog [G10a]SHa with a breast cancer targeting peptide (BCTP). The resulting peptide temporin [G10a]SHa-BCTP conjugate was selectively active against the MCF-7 breast cancer cell line with no cytotoxicity in NIH-3T3 fibroblasts. Unlike the natural product or [G10a]SHa, the conjugated peptide induced apoptosis, down regulating the expression of Bcl-2 and survivin and up regulating Bax and caspase-3.
Original languageEnglish
Pages (from-to)68-82
JournalPeptides
Volume106
Early online date6 Jul 2018
DOIs
Publication statusPublished - Aug 2018

Keywords

  • antimicrobial peptides
  • temporin-SHa analogs
  • breast cancer targeting peptide conjugate
  • apoptosis
  • Bcl-2
  • survivin
  • caspase-3

Cite this