141PD - Bacoside A induced Sub-G0 arrest and early apoptosis in human glioblastoma cell line U-87 MG through notch signaling pathway

Date 17 December 2016
Event ESMO Asia 2016 Congress
Session CNS tumours
Topics Basic Science
Central Nervous System Malignancies
Presenter Madhuri G S Aithal
Citation Annals of Oncology (2016) 27 (suppl_9): ix42-ix45. 10.1093/annonc/mdw578
Authors M.G.S. Aithal, R. Narayanappa
  • Department Of Biotechnology, Dayananda Sagar College of Engineering, 560078 - Bangalore/IN

Abstract

Background

Glioblastoma multiforme (GBM) is the most common and highly malignant brain tumor with a poor prognosis of less than a year despite advance treatment facilities. Among many cell signaling pathway genes that show genetic alterations, aberrant expression of Notch pathway genes occurs frequently in GBM thus presenting novel therapeutic targets. Various herbal products having anticancer properties are being used in adjuvant therapy that are nontoxic and affordable compared to highly toxic and expensive chemotherapeutics. Bacopa monnieri has been used in Ayurveda for brain cell development because of its neuroprotective properties. Its anticancer properties have proved to be promising in treating cancers.

Methods

This study is an attempt to evaluate the anticancer properties of Bacoside A, a component of Bacopa monnieri on GBM cell line U-87 MG and determine its effect on expression of Notch pathway genes. Flow cytometry analysis was carried out to study cell cycle arrest and apoptosis. Expression patterns of eight Notch pathway genes including Notch receptors (Notch1, Notch2, Notch3 and Notch4), ligands (Jagged1and Jagged2), downstream target (HES1) and a component of gamma-secretase complex (APH1A) were studied by quantitative real-time PCR.

Results

Bacoside A showed considerable cytotoxicity on U-87 MG cell line causing cell cycle arrest and apoptosis. Cell cycle analysis showed an appreciable arrest of 39.21% cells in Sub-G0 phase at 80µg/ml concentration, further increasing to 53.21% at the higher concentration of 100µg/ml. The percentage of early apoptotic cells was low (3.48%) for untreated cells which increased substantially to 31.36% and 41.11% after 80µg/ml and 100µg/ml of Bacoside A treatment respectively. Further, the expression of Notch1 gene decreased with a fold change of 0.05 after exposure to Bacoside A, whereas the expression of HES1 gene increased by 25 fold.

Conclusions

These data suggest that Bacoside A has a potential anticancer activity inducing cell cycle arrest and apoptosis via Notch signaling pathway in GBM in vitro.

Clinical trial indentification

Not applicable.

Legal entity responsible for the study

Department of Science and Technology

Funding

Department of Science and Technology

Disclosure

All authors have declared no conflicts of interest.