BACKGROUND: Calreticulin (CRT), an endoplasmic reticulum-resident protein 
generally overexpressed in cancer cells, is associated with radiation 
resistance. CRT shows higher transacetylase activity, as shown by us earlier, in 
the presence of the polyphenolic acetates (like 7, 8-diacetoxy-4-methylcoumarin, 
DAMC) and modifies the activity of a number of proteins, thereby influencing 
cell signaling.
AIM: To investigate the relationship between CRT expression and radiation 
response in a human glioma cell line and to evaluate the radiomodifying effects 
of DAMC.
METHODS AND RESULTS: Studies were carried out in an established human glioma 
cell line (BMG-1) and its isogenic clone overexpressing CRT (CROE, 
CRT-overexpressing cells) by analyzing clonogenic survival, cell proliferation, 
micronuclei analysis, and protein levels by Western blotting as parameters of 
responses. CRT overexpression conferred resistance against radiation-induced 
cell death in CROE cells (D37  = 7.35 Gy, D10  = 12.6 Gy and D0  = 7.25 Gy) as 
compared to BMG-1 cells (D37  = 5.70 Gy, D10  = 9.2 Gy and D0  = 5.6 Gy). A 
lower level of radiation-induced micronuclei formation observed in CROE cells 
suggested that reduced induction and/or enhanced DNA repair partly contributed 
to the enhanced radioresistance. Consistent with this suggestion, we noted that 
CRT-mediated radioresistance was coupled with enhanced grp78 level and reduced 
P53 activation-mediated prodeath signaling, while no changes were noted in 
acetylation of histone H4. DAMC-enhanced radiation-induced delayed (secondary) 
apoptosis, which was higher in CROE cells.
CONCLUSION: CRT overexpression confers resistance against radiation-induced 
death of human glioma cells, which can be overcome by the polyphenolic acetate 
DAMC.