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Updated: Jun 23, 2025

Activation of Apoptosis by Cytoplasmic Microinjection of Cytochrome c
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Hirocidins, Cytotoxic Metabolites from Streptomyces hiroshimensis, Induce Mitochondrion-Mediated Apoptosis

Esther J Han1, Myungeun Jeong1, Seoung Rak Lee2

  • 1Department of Chemistry, Princeton University, Princeton, NJ 08544, USA.

Angewandte Chemie (International Ed. in English)
|June 19, 2024
PubMed

Insights

Researchers discovered hirocidins, novel compounds from Streptomyces hiroshimensis, exhibiting antiproliferative effects against cancer cells. These molecules induce apoptosis, offering new avenues for anticancer drug discovery.

Area of Science:

  • Microbiology
  • Natural Products Chemistry
  • Pharmacology

Background:

  • Whole genome sequencing reveals significant untapped microbial potential for therapeutic small molecule production.
  • Exploring known antimicrobial producers with novel assays can uncover new bioactive compounds.

Purpose of the Study:

  • To discover novel secondary metabolites with antiproliferative activity from microbial sources.
  • To characterize the chemical structures and biological activities of newly identified compounds.

Main Methods:

  • Utilized alternative antiproliferative assays against persistent cancer cell lines.
  • Isolated and characterized novel secondary metabolites using spectroscopic methods.
  • Investigated the mode of action, including apoptosis induction and caspase-9 involvement.

Main Results:

  • Discovered hirocidins, novel secondary metabolites from Streptomyces hiroshimensis.
  • Demonstrated antiproliferative activity of hirocidins against colon and persistent breast cancer cells.
  • Identified unique chemical structures: hirocidin A (carbocyclic maleimide) and hirocidins B/C (bridged azamacrocyclic backbone).
  • Showed hirocidins induce mitochondrion-dependent apoptosis via caspase-9 activation.

Conclusions:

  • Hirocidins represent a new class of cytotoxins with potential in anticancer drug discovery.
  • The unique scaffolds of hirocidins contribute to chemical diversity for drug development.
  • Understanding the mode of action and synthetic routes facilitates further investigation of hirocidin targets.
Keywords:
Antiproliferative MetabolitesCaspase-9Mitochondrion-dependent ApoptosisNatural ProductsStreptomyces hiroshimensis

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