Natural bioactive gallic acid shows potential anticancer effects by inhibiting the proliferation and invasiveness behavior in human embryonic carcinoma cells

Embryonic cancer stem cells (CSCs), referred to as self‑renewable cells, are commonly found in liquid and solid cancers and can also be attributed to tumor onset, resistance, expansion, recurrence and metastasis following treatment. Cancer therapy targeting CSCs using natural bioactive products is an optimal option for inhibiting cancer recurrence, thereby improving prognosis. Several natural compounds and extracts have been used to identify direct or indirect therapy effects that reduce the pathological activities of CSCs. Natural gallic acid (GA) is noted to have anticancer properties for oncogene expression, cycle arrest, apoptosis, angiogenesis, migration and metastasis in various cancers. The present study demonstrated that GA has various anticancer activities in NTERA‑2 and NCCIT human embryonic carcinoma cells. In two types of embryonic CSCs, GA effectively induced cell death via late apoptosis. Furthermore, GA showed the G0/G1 cell cycle arrest activity in embryonic CSCs by inducing the increase of p21, p27 and p53 expression and the decrease of CDK4, cyclin E and cyclin D1 expression. The present study showed that GA inhibited the expression levels of mRNA and protein for stem cell markers, such as SOX2, NANOG and OCT4, in NTERA‑2 and NCCIT cells. The induction of cellular and mitochondrial reactive oxygen species by GA also activated the cellular DNA damage response pathway by raising the phosphorylated‑BRCA1, ATM, Chk1, Chk2 and histone. Finally, GA inhibited CSCs invasion and migration by inhibiting the expression of matrix metalloproteinase by the downregulation of EGFR/JAK2/STAT5 signaling pathway. Thus, it is hypothesized that GA could be a potential inhibitor of cancer emergence by suppressing CSC properties.