DOI: 10.4103/bbrj.bbrj_59_26 ISSN: 2588-9834

Combined Lethal-7b microRNA and Fengycin Treatment Selectively Reduces Cell Viability and Modulates Apoptosis-related Gene Expression in Human Lung Adenocarcinoma (A549) Cells

Yaser Jasem Alkhatony, Mahmood Abdujabar Altobje, Mahmood Ahmad Aboo
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Abstract

Background:

The present study was designed to evaluate the effects of combined lethal-7b microRNA (Let-7b) and fengycin treatment on cell viability and cytotoxicity in human lung adenocarcinoma cell line (A549) lung cancer cells.

Methods:

Fengycin was obtained from a commercial supplier and prepared at different concentrations. Its cytotoxic activity, alone and in combination with Let-7b, was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay in A549 lung cancer cells and normal human gingival fibroblast (HGF) cells at concentrations of 20, 30, and 40 μg/ml. In addition, the expression levels of selected genes, including K-ras , Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha ( PIK3CA ), Tumor Protein p53 ( TP53 ), and Caspase-3 , were analyzed by reverse transcription quantitative polymerase chain reaction.

Results:

Treatment with fengycin resulted in a clear dose-related increase in cytotoxicity in A549 cells, reaching 5%, 67%, and 65.7% at 20, 30, and 40 μg/ml, respectively ( P = 0.001). In contrast, only minor effects were observed in HGF cells (3%, 1%, and 4%; P = 0.853). Transfection with Let-7b alone led to a noticeable increase in cytotoxicity in A549 cells (57.6%), while HGF cells showed relatively low sensitivity (17%). The combined treatment (Let-7b/fengycin co-treatment; 40 μg/mL fengycin and 2.5 nM microRNAs) produced high cytotoxicity in A549 cells (76.3%) while preserving HGF cell viability, with only 2.7% cytotoxicity in HGF cells ( P < 0.001). At the molecular level, this treatment was associated with upregulation of TP53 , Caspase-3 , and PIK3CA (1.88, 2.85, and 1.08-fold, respectively), along with marked downregulation of K-ras (0.56-fold). In contrast, HGF cells showed downregulation of K-ras (0.91-fold), minimal changes in apoptosis-related markers (Caspase-3: 1.15-fold; TP53: 0.94-fold), and upregulation of PIK3CA (2.2-fold).

Conclusion:

The Let-7b/fengycin co-treatment exhibited selective cytotoxic activity against A549 lung cancer cells while largely preserving HGF cell viability, highlighting its potential as a promising anticancer strategy that warrants further investigation.

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