Objective  To investigate whether puerarin (PRN) synergizes with arsenic trioxide (As₂O₃) in facilitating the apoptosis of human glioblastoma cell line U87 through the protein kinase (Akt)/p 38 mitogen-activated protein kinases (p38-MAPK) pathway.

  Methods  The 3-(4, 5-deimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide technique was performed to detect cell survival. Flow cytometry was applied to calculate cell apoptosis, and immunoblot technique was used to verify the protein expressions of phosphorylated Akt, p38-MAPK, and cleaved caspase-3. In addition, caspase-3 mRNA levels were detected by real-time polymerase chain reaction.

  Results  PRN synergized with As₂O₃ to decrease the survival of human glioblastoma cell line U87. A single dosage each of PRN (16 µM; 1.13±0.015) and As₂O₃ (2 µM; 1.18±0.33) significantly increased the intracellular calcium concentration. Moreover, PRN synergized with As₂O₃ to increase the intracellular calcium concentration (1.34±0.72) compared with the findings in the As₂O₃ only group. The synergy of PRN and As₂O₃ significantly downregulated phosphorylated Akt expression, as well as upregulated the levels of phosphorylated p38-MAPK, cleaved caspase-3 proteins, and caspase-3 mRNA.

  Conclusion  PRN synergized with As₂O₃ to increase intracellular calcium and inhibit cell survival. In addition, PRN synergized with As₂O₃ to repress phosphorylated Akt expression, as well as to upregulate phosphorylated p38-MAPK and cleaved caspase-3 protein levels, thereby contributing to cell apoptosis. Clinically, PRN combined with As₂O₃ is a potential adjuvant drug for the treatment of malignant tumors.