BioScience Trends. 2019;13(1):40-48. (DOI: 10.5582/bst.2019.01006)

Effects of BENC-511, a novel PI3K inhibitor, on the proliferation and apoptosis of A549 human lung adenocarcinoma cells.

Tian HQ, Zhang Y, Zhang QY, Li SX, Liu Y, Han XZ

The small chemical compound 8-ethoxy-2-(4-fluorophenyl)-3-nitro-2H-chromene (S14161) was recently identified as an inhibitor of phosphoinositide 3-kinase (PI3K) and reported to inhibit tumor growth. However, its chiral structure and poor solubility prevent its further use. Compound 6-bromo-8-ethoxy-3-nitro-2H-chromene (BENC-511) is an analogue of S14161 produced by structural optimization. A previous study indicated that BENC-511 acted on multiple myeloma and that it had a toxicity by inhibiting the PI3K/protein kinase B (Akt) pathway. However, the effects of BENC-511 on the proliferation and apoptosis of A549 human lung adenocarcinoma cells have not been reported. The current study investigated the effects of BENC-511 on the proliferation and apoptosis of A549 cells in vitro. Results indicated that the compound BENC-511 inhibited the viability of A549 cells in a concentration- and timedependent manner. BENC-511 suppressed proliferation and colony formation via S phase arrest. BENC-511 decreased the expression of cyclin A, proliferating cell nuclear antigen (PCNA), B-cell lymphoma-2 (Bcl-2), phospho-mammalian target of rapamycin (p-mTOR), and phospho-Akt (p-Akt) and it increased the expression of p21WAF1CIP1(p21), Caspase-3 and Caspase-9. In conclusion, BENC-511 inhibited the proliferation of A549 human lung adenocarcinoma cells via S phase arrest as a result of up-regulation of p21 and reduction of Cyclin A/cyclin-dependent kinase 2 (CDK2)/PCNA complex and it induced apoptosis by reducing the mitochondrial membrane potential via the Akt/Bcl-2/Caspase-9 mitochondrial pathway of apoptosis.

Full Text: