Apoptosis

, Volume 13, Issue 1, pp 119–131 | Cite as

Myrtucommulone from Myrtus communis induces apoptosis in cancer cells via the mitochondrial pathway involving caspase-9

  • Irina Tretiakova
  • Dagmar Blaesius
  • Lucia Maxia
  • Sebastian Wesselborg
  • Klaus Schulze-Osthoff
  • Jindrich CinatlJr
  • Martin Michaelis
  • Oliver Werz
Original Paper

Abstract

Myrtucommulone (MC) is a unique, nonprenylated acylphloroglucinol contained in the leaves of myrtle (Myrtus communis). Here, we addressed the potential of MC to induce apoptosis of cancer cells. MC potently induced cell death of different cancer cell lines (EC50 3–8 μM) with characteristics of apoptosis, visualized by the activation of caspase-3, -8 and -9, cleavage of poly(ADP-ribose)polymerase (PARP), release of nucleosomes into the cytosol, and DNA fragmentation. MC was much less cytotoxic for non-transformed human peripheral blood mononuclear cells (PBMC) or foreskin fibroblasts (EC50 cell death = 20–50 μM), and MC up to 30 μM hardly caused processing of PARP, caspase-3, -8 and -9 in human PBMC. MC-induced apoptosis was mediated by the intrinsic rather than the extrinsic death pathway. Thus, MC caused loss of the mitochondrial membrane potential in MM6 cells and evoked release of cytochrome c from mitochondria. Interestingly, Jurkat cells deficient in caspase-9 were resistant to MC-induced cell death and no processing of PARP or caspase-8 was evident. In cell lines deficient in either CD95 (Fas, APO-1) signalling, FADD or caspase-8, MC was still able to potently induce cell death and PARP cleavage. Conclusively, MC induces apoptosis in cancer cell lines, with marginal cytotoxicity for non-transformed cells, via the mitochondrial cytochrome c/Apaf-1/caspase-9 pathway.

Keywords

Cancer Apoptosis Mitochondria Caspase Myrtucommulone 

Abbreviations

CHX

Cycloheximide

FADD

Fas-associated death domain

IBP-C

Isobutyrophenone core

5-LO

5-Lipoxygenase

MC

Myrtucommulone

ΔΨm

Mitochondrial membrane potential

MM6

Mono Mac 6

PARP

Poly(ADP-ribose)polymerase

PBMC

Peripheral blood mononuclear cells

S-MC

Semi-myrtucommulone

TNF

Tumour necrosis factor

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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Irina Tretiakova
    • 1
  • Dagmar Blaesius
    • 2
  • Lucia Maxia
    • 3
  • Sebastian Wesselborg
    • 4
  • Klaus Schulze-Osthoff
    • 5
  • Jindrich CinatlJr
    • 6
  • Martin Michaelis
    • 6
  • Oliver Werz
    • 2
  1. 1.Institute of Pharmaceutical ChemistryUniversity of FrankfurtFrankfurt am MainGermany
  2. 2.Department of Pharmaceutical Analytics, Pharmaceutical InstituteUniversity of TuebingenTuebingenGermany
  3. 3.COSMESECagliariItaly
  4. 4.Department of Internal Medicine IUniversity of TuebingenTuebingenGermany
  5. 5.Institute of Molecular MedicineHeinrich-Heine-UniversityDuesseldorfGermany
  6. 6.Institute of Medical VirologyUniversity Hospital FrankfurtFrankfurt am MainGermany

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