Inactivation of PI3K/Akt signaling mediates proliferation inhibition and G2/M phase arrest induced by andrographolide in human glioblastoma cells

摘要: Abstract Aims Andrographolide, a principal diterpenoid lactone isolated from the traditional herbal medicine Andrographis paniculata , has been reported to show anti-tumor activity. Since high lipid solubility of andrographolide permits it penetrate blood–brain barrier and concentrate in brain, we hypothesized that may be potential chemotherapeutic agent for treatment glioblastomas. To clarify this point, investigated growth inhibitory effect mechanisms actions on human glioblastoma U251 U87 cells. Main methods MTT assay trypan blue exclusion were used investigate proliferation cytotoxic effects andrographolide, respectively. Cell cycle distribution was analyzed using flow cytometry. Apoptosis analysis proceeded by detecting cleavage caspase-3. The levels proteins probed Western blotting. Key findings results showed non-toxic concentrations inhibited cells through induction G2/M arrest, which accompanied down-regulating Cdk1 Cdc25C proteins. Additionally, decreased activity PI3K/Akt signaling, as demonstrated down-regulation expression phos-PI3K, phos-Akt, phos-mTOR phos-p70s6k Furthermore, additive inhibition, arrest phase-related observed, when combined with PI3K inhibitor LY294002 Significance We prove inhibits via inducing is mediated inhibiting signaling.