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

Olivia M Tandrasasmita; Jason S Lee; Sung Hee Baek; Raymond R Tjandrawinata

doi:10.4161/cbt.10.8.13085

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.

Authors

Olivia M Tandrasasmita¹, Jason S Lee, Sung Hee Baek, Raymond R Tjandrawinata

Affiliation

¹ Molecular Pharmacology Group, Division of Molecular Pharmacology and Phytochemistry, Dexa Laboratories of Biomolecular Sciences, Dexa Medica Group, Cikarang, Indonesia.

PMID: 20703095
DOI: 10.4161/cbt.10.8.13085

Abstract

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*

Substances

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