Anticancer effect of Limonin against benzo(a)pyrene-induced lung carcinogenesis in Swiss albino mice and the inhibition of A549 cell proliferation through apoptotic pathway.

Abstract

The main purpose of the current study is to reveal the anticancer action of limonin against benzo(a)pyrene [B(a)P]-treated lung carcinogenesis in Swiss albino mice and A549 lung cancer cells. B(a)P was orally supplemented (50 mg/kg body weight) twice a week for four weeks induction of lung cancer in mice. The lung weight, body weight, incidence of tumor, lipid peroxidation, carcinoembryonic antigen (CEA), enzymatic and nonenzymatic antioxidants (superoxide dismutase, GPx, glutathione, glutathione reductase, catalase, and glutathione S-transferase), serum marker enzymes (aryl hydroxylase, lactate dehydrogenase, 5'-nucleotidases, and γ-glutamyl transpeptidase), and inflammatory mediators (interleukin-1β, interleukin-6, and tumor necrosis factor-α) were estimated. Moreover, a histopathological study of lung tissues was supported by the biochemical analysis. Furthermore, the anticancer activity of limonin on A549 cells was measured by cell viability, production of reactive oxygen species (ROS), apoptotic morphological changes by AO/EtBr staining. Additionally, the status of apoptosis protein (caspase-9 and -3) expressions was analyzed by the colorimetric analysis. B(a)P-induced mice showed increased lipid peroxidation, CEA, serum marker enzymes and inflammatory cytokines levels with simultaneously decreased in the nonenzymatic and enzymatic antioxidants levels. Limonin supplements significantly reverted back to all these changes in this manner, showing the efficiency of anticancer effect. Furthermore, our in vitro study also supported the anticancer effect of the treatment of limonin-enhanced apoptosis by loss of cell viability, improved ROS production, apoptotic morphological changes, and apoptosis protein expression were analyzed. Overall, these results suggest the anticancer potential of limonin against B(a)P-induced lung cancer in Swiss albino mice and A549 lung cancer cells.