This study elucidates the anti-
cancer potential of
gallic acid (GA) as a promising therapeutic agent that exerts its effect by regulating the PI3K/Akt pathway. To prove our research rationale, we used diverse experimental methods such as cell viability assay, colony formation assay,
tumor spheroid formation assay, cell cycle analysis, TUNEL assay, Western blot analysis, xenograft mouse model and histological analysis. Treatment with GA inhibited cell proliferation in dose-dependent manner as measured by cell viability assay at 48 h. GA and
cisplatin (CDDP) also inhibited colony formation and
tumor spheroid formation. In addition, GA and CDDP induced apoptosis, as determined by the distribution of early and late apoptotic cells and DNA fragmentation. Western blot analysis revealed that inhibition of the PI3K/Akt pathway induced upregulation of
p53 (tumor suppressor protein), which in turn regulated cell cycle related
proteins such as p21, p27,
Cyclin D1 and E1, and intrinsic apoptotic
proteins such as Bax, Bcl-2 and cleaved
caspase-3. The anti-
cancer effect of GA was further confirmed in an in vivo mouse model.
Intraperitoneal injection with GA for 4 weeks in an A549-derived
tumor xenograft model reduced the size of
tumor mass. Injection of them downregulated the expression of
proliferating cell nuclear antigen and p-Akt, but upregulated the expression of cleaved
caspase-3 in
tumor tissues. Taken together, these results indicated that GA hindered
lung cancer progression by inducing cell cycle arrest and apoptosis, suggesting that GA would be a potential therapeutic agent against
non-small cell lung cancer.