Induction of cellular apoptosis in human breast cancer by DLBS1425, a Phaleria macrocarpa compound extract, via down-regulation of PI3-kinase/AKT pathway.
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.
Tandrasasmita
Olivia M
OM
Molecular Pharmacology Group, Division of Molecular Pharmacology and Phytochemistry, Dexa Laboratories of Biomolecular Sciences, Dexa Medica Group, Cikarang, Indonesia.
Lee
Jason S
JS
Baek
Sung Hee
SH
Tjandrawinata
Raymond R
RR
D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D045325:HCT116 Cells; D056945:Hep G2 Cells; D006801:Humans; D015151:Immunoblotting; D015394:Molecular Structure; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D029645:Thymelaeaceae / Q000737:chemistry*
D051017:Apoptosis Regulatory Proteins; C558638:DLBS 1425; D010936:Plant Extracts; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt