Induction of cellular apoptosis in human breast cancer by DLBS1425, a Phaleria macrocarpa compound extract, via down-regulation of PI3-kinase/AKT pathway

Cancer Biol Ther. 2010 Oct 15;10(8):814-23. doi: 10.4161/cbt.10.8.13085. Epub 2010 Oct 15.


Phaleria macrocarpa, also known as Mahkota dewa, is an Indonesian native plant that has been used as a remedy for many diseases. However, the molecular mechanism of Phaleria macrocarpa is still limited. In this study, we evaluate its molecular mechanism using a bioactivity-guided DLBS1425, an extract of Phaleria macrocarpa on MDA-MB-231 breast cancer cell line. DLBS1425 exhibited inhibition of proliferative, migratory and invasive potential of MDA-MB-231 in a dose-dependent manner, and significantly reduced phosphoinositide-3 (PI3)-kinase/protein kinase B (AKT) signalling by reducing PI3K transcript level and subsequent reduction in AKT phosphorylation. Further, it induced pro-apoptotic genes including BAX, BAD and PUMA and consequently induces cellular death signal by caspase-9 activation, promoting PARP cleavage and DNA fragmentation. Our results suggest that DLBS1425 is a potential anticancer agent which targets genes involved in both cell survival and apoptosis in MDA-MB-231 breast cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Cycle / drug effects
  • Cell Line
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Down-Regulation / drug effects
  • Female
  • Flow Cytometry
  • Gene Expression Regulation, Neoplastic / drug effects
  • HCT116 Cells
  • Hep G2 Cells
  • Humans
  • Immunoblotting
  • Molecular Structure
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphorylation / drug effects
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / drug effects*
  • Thymelaeaceae / chemistry*


  • Apoptosis Regulatory Proteins
  • DLBS 1425
  • Plant Extracts
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt