title: Methyl gallate isolated from Spondias pinnata exhibits anticancer activity against human glioblastoma by induction of apoptosis and sustained extracellular signal-regulated kinase 1/2 activation.
abstract: BACKGROUND
  Spondias pinnata has been reported for its efficient anticancer effects, but the studies were mostly focused on its extract.
  
  
  OBJECTIVE
  Since its bioactive compounds are largely unknown, this study was designed to characterize the lead components present in it and their anticancer activity against human glioblastoma cell line (U87).
  
  
  METHODS
  Major compounds from the ethyl acetate fraction were isolated by column chromatography and their anticancer potentials against U87 cells were evaluated. Furthermore, flow cytometric and immunoblotting analyses were performed to demonstrate the mechanism of apoptosis inducing activity of methyl gallate (MG) against U87 cell line.
  
  
  RESULTS
  Four major compounds were isolated from the ethyl acetate fraction. Amongst these, two compounds showed promising activities and with the help of different spectroscopic methods they were identified as gallic acid and MG. Flow cytometric studies revealed that MG-induced apoptosis in U87 cells dose-dependently; the same was confirmed by activation of caspases through cleavage of endogenous substrate poly (adenosine diphosphate-ribose) polymerase. MG treatment also induced the expression of p53 and B-cell lymphoma-2-associated X and cleavage of BH3 interacting-domain with a concomitant decrease in B-cell lymphoma-2 expression. Moreover, MG-induced sustained phosphorylation of extracellular signal-regulated kinase (ERK1/2) in U87 cells with no change in the phosphorylation of other mitogen-activated protein kinases (c-Jun N-terminal of stress-activated protein kinases, p38).
  
  
  CONCLUSIONS
  MG is a potent antioxidant and it induces sustained ERK1/2 activation and apoptosis in human glioblastoma U87, and provide a rationale for evaluation of MG for other brain carcinoma cell lines for the advancement of glioblastoma therapy.
authors.affiliation: Division of Molecular Medicine, Bose Institute, Kolkata, West Bengal, India.
authors.forename: Dipankar
authors.initials: D
authors.lastname: Chaudhuri
authors.affiliation: Division of Molecular Medicine, Bose Institute, Kolkata, West Bengal, India.
authors.forename: Nikhil Baban
authors.initials: NB
authors.lastname: Ghate
authors.affiliation: Division of Chemistry, TCG Life Sciences Limited, Kolkata, West Bengal, India.
authors.forename: Sudhir Shankar
authors.initials: SS
authors.lastname: Singh
authors.affiliation: Division of Molecular Medicine, Bose Institute, Kolkata, West Bengal, India.
authors.forename: Nripendranath
authors.initials: N
authors.lastname: Mandal
keywords: Anticancer; Spondias pinnata; U87; apoptosis; cytotoxicity; methyl gallate
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