Jatuporn Polhiran

Background: Non-small-cell lung cancer (NSCLC) is a major cause of cancer-related mortality. Current therapies are limited by drug resistance and adverse effects, highlighting the need for new strategies. Panduratin A (PA), a chalcone from Boesenbergia rotunda, has reported anticancer activity. This study investigated the effects of PA in NSCLC cells and whether PA enhances tumor necrosis factor alpha (TNF-α)-associated cell death. Methods: Human NSCLC cell lines A549 and H1299 were treated with PA alone or in combination with TNF-α. Cytotoxicity and apoptosis were assessed using cell-viability assays, cell-number analysis, and flow cytometry. Western blotting was used to evaluate caspase-3 activation and PARP-1 cleavage. Cell-cycle distribution was analyzed to determine the impact of PA on cell-cycle progression. Results: PA reduced cell number and induced cell death in both A549 and H1299 cells, and co-treatment with TNF-α increased apoptosis compared with single-agent treatment. PA increased the G1-phase fraction and, in a concentration-dependent manner, reduced expression of thymidine kinase and cyclin A2, consistent with a G1-associated arrest phenotype. Combination treatment also increased the sub-G1 population. Conclusions: PA promotes apoptosis in NSCLC cells and enhances TNF-α-associated apoptotic cell death in vitro, accompanied by a G1-associated cell-cycle phenotype. These findings provide an in vitro framework for studying natural compounds as modulators of TNF-α-driven apoptosis and support further mechanistic validation in more disease-relevant models.

Lung cancer remains the leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) accounting for the majority of cases and frequently associated with poor outcomes due to resistance to conventional therapies. The epidermal growth factor (EGF)–epidermal growth factor receptor (EGFR) axis plays a central role in NSCLC progression by activating downstream phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) signaling, thereby promoting survival and proliferation. Natural compounds have emerged as promising modulators of these pathways, and oxyresveratrol (OXY), a hydroxylated analog of resveratrol, has been reported to possess antioxidant and anticancer properties, though its mechanistic role in NSCLC remains unclear. In this study, we investigated the effects of OXY in EGF-stimulated A549 and H1299 cells. OXY significantly reduced metabolic activity and decreased cell number in a dose-dependent manner and increased the proportion of apoptotic cells. Mechanistically, OXY selectively attenuated EGF-induced AKT phosphorylation while largely sparing extracellular signal–regulated kinase 1/2 (ERK1/2) activation and did not measurably alter EGFR phosphorylation or receptor trafficking dynamics. These findings indicate that OXY exposure is associated with AKT-selective signaling suppression and reduced cellular fitness in NSCLC cells, without evidence of direct EGFR inhibition. Further genetic rescue and pathway-epistasis studies are required to establish causal dependency on AKT signaling and to support in vivo validation.