Peiminine Alleviates Breast Carcinoma via Reprogramming the PI3K/Akt/mTOR Pathway in vitro and in vivo

Background

The breast cancer is most frequently diagnosed cancer in the women worldwide. Our study investigated the anticancer effect of peiminine, an alkaloid obtained from Fritillaria thunbergii, against breast carcinoma.

Materials and Methods

The toxicity study investigated LD₅₀ and the subsequent doses of peiminine for carcinogenic study. The in vitro chemotherapeutic assessment was performed on MCF7 cells through MTT assay and flow cytometry. The breast cancer was developed in rats via induction of DMBA (5 mg/kg, i.v.) and sustained for 24 weeks. The induction of breast cancer and the chemotherapeutic effect of peiminine were assessed through histopathological analysis of rat mammary tissue, followed by immunohistochemical analysis, cell proliferation assay and apoptosis assay by TUNEL method.

Results

The IC₅₀ value of peiminine in MCF7 cell was found to be 5 μg/mL which demonstrate a significant induction of apoptosis and enhanced caspase-3 expression in MCF7 cells in a dose dependent manner. The complex also caused cell cycle arrest at S phase and G2/M phase dose dependently. Additionally, peiminine therapy decreased the hyperplastic lesions of mammary tissue and restored the normal histopathological characteristics of breast tissue. Furthermore, peiminine treatment downregulated the expression of carcinogenic markers such as PI3K and Akt increased the expression of apoptotic markers including p53 and Bax. Peiminine therapy also decreased the cellular proliferation and enhanced the apoptotic events.

Conclusion

In conclusion, the breast cancer progression was significantly reduced via induction of apoptotic events and inhibition of cell propagation which allowed constructing of suitable mechanism for peiminine mediated chemotherapeutic approach.