Invitro Study of Antitumor Activity of Alogliptin in Lung Cancer Cell Line (A549)

Background: Lung cancer is still the leading cause of cancer-related deaths globally. However, many conventional treatments are associated with high toxicity and limited selectivity for cancer cells. This condition highlights the urgent need for novel therapeutic agents with enhanced anticancer potential and reduced adverse effects on healthy tissues. Dipeptidyl peptidase-4 (DPP4) inhibitors have emerged as promising candidates for various malignancies, including colorectal, prostate, and renal cancers, due to their remarkable anticancer properties. 
Objectives: This study evaluated the cytotoxic and anticancer activity of alogliptin (Alo), a selective DPP4 inhibitor, against the human lung cancer A549 cell line and normal breast epithelial HBL100 cells, as monotherapy and in combination with cisplatin (Cis).
Methods: Each type of cell (A549 cell and normal HBL100 cell) was divided into four groups: untreated control, Cis-treated, Alo-treated, and Cis+Alo-treated. After 72 hours of incubation, cell viability was assessed using the MTT (3-[4,5-dimethylthiazol-2-yl] -2,5-diphenyl tetrazolium bromide) assay to determine the half-maximal inhibitory concentration (IC50). This method is safe, more reproducible, and uses test cell viability and cytotoxicity endpoints. Following IC50-based treatment, apoptotic markers, including BCL2 and survivin expression levels, were evaluated.  
Results: MTT assay showed that both Cis and Alo significantly decreased A549 cell viability (P<0.0001). Alo therapy clearly increased inhibition of A549 cells compared with the control, but showed lower cytotoxicity toward normal HBL100 cells (cytotoxic only at higher concentrations), yielding results comparable to those of Cis. The combination of Cis and Alo demonstrated a dose-dependent cytotoxic effect on A549 lung adenocarcinoma cells, with significant anticancer activity observed at higher concentrations. However, the combination of Alo and Cis did not significantly increase cytotoxicity against A549 cells compared with Cis alone. Furthermore, exposing A549 cells to Alo alone significantly decreased BCL2 levels compared with Cis alone (P<0.001). The results further showed that after treating A549 cells with an IC50 of Alo, there was a significant decrease in survivin levels (P<0.0001) compared with control cells.
Conclusion: Alo, a DPP-4 inhibitor, demonstrated anticancer effects against A549 cells as evidenced by the MTT assay and by changes in BCL2 and survivin expression, indicating its potential anticancer activity against this cancer cell line. Although Alo exhibited dramatic pro-apoptotic activity, as indicated by reduced BCL2 and survivin levels, when combined with Cis, no clear synergism was observed.