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Objective. Gastric cancer, one of the most common malignant tumors worldwide, arises from the gastric mucosal epithelium and severely affects patient health and quality of life. Luteolin (LUT) is a flavonoid found in vegetables and fruits with diverse functions. A large number of studies have confirmed that LUT has an antitumor effect. Therefore, this study is aimed at verifying whether LUT can exert antitumor effects in synergy with oxaliplatin (OXA). As such, we examined the effects of LUT, OXA, and their coadministration in a gastric adenocarcinoma cell line (SGC-7901). We used the MTT assay to quantify the proliferation of SGC-7901 cells, flow cytometry to detect the cell cycle and apoptosis, ELISA to detect the expression of cell-cycle-related proteins, and western blot to detect the expression of related apoptotic factors. The results of this study show that the combination of LUT and OXA inhibited SGC-7901 cell proliferation and induced apoptosis by altering cell-cycle proportions. In addition, the combination also activated Cyt c/caspase signaling in SGC-7901 cells. In summary, LUT synergy with OXA inhibited the proliferation of gastric cancer cells in vitro. The present study also elucidated the mechanism by which LUT potentiated the sensitivity of SGC-7901 cells to OXA through the Cyt c/caspase pathway. [ABSTRACT FROM AUTHOR]

• Cucurbitacin IIb (CuIIb) exhibited the proliferation inhibitory activity in A549 cells. • CuIIb induced apoptosis via STAT3 pathway. • CuIIb suppressed the cell cycle and resulted G2/M phase cell cycle arrest. • Leu694 and Met769 are key amino acids for EGFR-CuIIb binding. • CuIIb inhibited the kinase activity of EGFR and may serve as a potential EGFR TKI. Epidermal growth factor receptor (EGFR) is considered as a valid target in the clinical trials of anticancer therapy and tyrosine kinase inhibitors (TKIs) of EGFR are approved for cancer treatments. In present work, cucurbitacin IIb (CuIIb) was confirmed to exhibit the proliferation inhibitory activity in A549 cells. CuIIb induced apoptosis via STAT3 pathway, which was mitochondria-mediated and caspase-dependent. CuIIb also suppressed the cell cycle and induced G2/M phase cell cycle arrest. CuIIb was capable of suppressing the signal transmitting of the EGFR/mitogen-activated protein kinase (MAPK) pathway which was responsible for the apoptosis and cell cycle arrest. Homogeneous time-resolved fluorescence (HTRF) analysis demonstrated that the kinase activity of EGFR was inhibited by CuIIb. Molecular docking suggested that the CuIIb-EGFR binding fundamentally depends on the contribution of both hydrophobic and hydrogen-bonding interactions. Hence CuIIb may serve as a potential EGFR TKI. [ABSTRACT FROM AUTHOR]