GGC promoted the expression of PTPε protein.
To study the mechanism of GGC-mediated inhibition of STAT3
phosphorylation, we elucidated the impact of GGC by modulating of
protein tyrosine phosphatase. Pretraetment with sodium pervanadate
abrogated reduction in p-STAT3 levels caused by GGC (Fig. 2E). Moreover,
we noted that GGC led to a dramatic increase in PTPε protein levels
(Fig. F) however at mRNA level an augmentation was noted only in PTPε M,
but not PTPε C. Moreover, in A549 cells with PTPε siRNA, PTPε expression
was substantially reduced ((Fig. 2H) and GGC was unable to affect STAT3
phosphorylation in PTPε knockdown cells (Fig. 2I). In addition, PTPε
knockdown attenuated GGC-induced PARP cleavage suggesting that this
phosphatase may have a vital role in regulating anti-cancer properties
of GCC.