Neferine Inhibits 7,12-Dimethylbenz(a)anthracene-Induced Mammary Tumorigenesis by Suppression of Cell Proliferation and Induction of Apoptosis via Modulation of the PI3K/AKT/NF-κB Signaling Pathway
Aim. To investigate the anticancer mechanism of neferine on DMBA prompted mammary tumorigenesis in animals. Methods. Mammary cancer was prompted by the subcutaneous injection of 25 mg DMBA mixed in 1 ml of the vehicle [sunflower oil (0.5 ml) and saline (0.5 ml)]. We analyzed the biochemical and molecular expression of cell-proliferation and apoptotic markers in normal and DMBA induced rats. Results. We detected low body weight, elevated quantities of lipid peroxidation, and low antioxidant enzyme activities in mammary tissues of DMBA-induced animals. We also found an invasive ductal carcinoma in DMBA-induced animals by histopathological assessment. Furthermore, western blotting findings were displaying an augmented expression of PI3K, AKT, NF-κB, PCNA, cyclin D1, Ki-67, and Bcl-2, while reducing expression of p53, Bax, caspase-3, and -9 in DMBA-induced cancer-bearing animals. RT-PCR results found an up-regulated cyclin D1, PCNA, Ki-67 and reduced expression of p53 in DMBA prompted animals. The oral administration of neferine effectually inhibited mammary tumors by the improved antioxidants and prevent lipid peroxidation activities when compared with tumor-bearing rats. Furthermore, neferine also modulated the PI3K/AKT/NF-κB signaling through inhibiting cell proliferation and induce apoptosis in tumor-bearing rats. Conclusion: In our findings, we concluded that neferine has anti-proliferative and enhancing apoptotic property against DMBA-induced mammary cancer.