Scutellarein (SCU), a
flavone that belongs to the
flavonoid family and abundantly present in Scutellaria baicalensis a flowering plant in the family Lamiaceae, has been reported to exhibit anticancer effects in several
cancer cell lines including
gastric cancer (GC). Although our previous study documented the mechanisms of Scutellarein‑induced cytotoxic effects, the literature shows that the proteomic changes that are associated with the cellular response to SCU have been poorly understood. To avoid adverse side‑effects and significant toxicity of
chemotherapy in patients who react poorly,
biomarkers anticipating therapeutic responses are imperative. In the present study, we utilized a comparative proteomic analysis to identify
proteins associated with
Scutellarein (SCU)‑induced cell death in GC cells (AGS and SNU484), by integrating two‑dimensional gel electrophoresis (2‑DE), mass spectrometry (MS), and bioinformatics to analyze the
proteins. Proteomic analysis between SCU‑treated and
DMSO (control) samples successfully identified 41 (AGS) and 31 (SNU484)
proteins by MALDI‑TOF/MS analysis and protein database search. Comparative proteomics analysis between AGS and SNU484 cells treated with SCU revealed a total of 7
protein identities commonly expressed and western blot analysis validated a subset of identified critical
proteins, which were consistent with those of the 2‑DE outcome. Molecular docking studies also confirmed the binding affinity of SCU towards these critical
proteins.
Phosphatidylinositol 4,5‑bisphosphate 3‑kinase catalytic subunit β
isoform (PIK3CB)
protein expression was accompanied by a distinct group of cellular functions, including cell growth, and proliferation. Cancerous inhibitor of
protein phosphatase 2A (CIP2A), is one of the oncogenic molecules that have been shown to promote
tumor growth and resistance to apoptosis and senescence‑inducing
therapies. In the present study, both PIK3CB and CIP2A
proteins were downregulated in SCU‑treated cells, which boosts our previous results of SCU to induce apoptosis and inhibits GC cell growth by regulating these critical
proteins. The comparative proteomic analysis has yielded candidate
biomarkers of response to SCU treatment in GC cell models and further validation of these
biomarkers will help the future clinical development of SCU as a novel therapeutic drug.