Lung cancer is the most often reported
cancer with a terrible prognosis worldwide.
Flavonoid metal complexes have exhibited potential chemotherapeutic effects with substantially low adverse effects. This study investigated the chemotherapeutic effect of the
ruthenium biochanin-A complex on lung
carcinoma in both in vitro and in vivo model systems. The synthesized organometallic complex was characterized via UV‒visible spectroscopy, FTIR, mass spectrometry, and scanning electron microscopy. Moreover, the
DNA binding activity of the complex was determined. The in vitro chemotherapeutic assessment was performed on the A549 cell line through MTT assay, flow cytometry, and western blot analysis. An in vivo toxicity study was performed to determine the chemotherapeutic dose of the complex, and subsequently, chemotherapeutic activity was assessed in benzo-α-
pyrene-induced
lung cancer mouse model by evaluating the histopathology, immunohistochemistry, and TUNEL assays. The IC50 value of the complex in A549 cells was found to be 20 µM. The complex demonstrated significant apoptosis induction, enhanced
caspase-3 expression and cell cycle arrest with downregulated PI3K, PPARγ, TGF-β, and TNF-α expression in A549 cells. The in vivo study suggested that
ruthenium biochanin-A therapy restored the morphological architecture of lung tissue in a benzo-α-
pyrene-induced
lung cancer model and inhibited the expression of Bcl2. Additionally, increased apoptotic events were identified with upregulation of
caspase-3 and p53 expression. In conclusion, the
ruthenium biochanin-A complex successfully amelioratedlung
cancer incidence in both in vitro and in vivo models through the alteration of the TGF-β/PPARγ/PI3K/TNF-α axis with the induction of the p53/
caspase-3-mediated apoptotic pathway.