Polyporus umbellatus inhibited tumor cell proliferation and promoted tumor cell apoptosis by down-regulating AKT in breast cancer.

Abstract

Breast cancer (BC) is the foremost cause of cancer-related mortality in women worldwide. Polyporus umbellatus is a polysaccharide preparation of the Chinese traditional herb medicine, which has been explored as an inhibitory compounds in suppressing many cancers. And AKT has been known as an essential signaling pathway to regulate cell proliferation and apoptosis via Mdm2/p53 and Caspase-3 signaling pathways respectively. In our study, western blot, RT-PCR, immunochemical assay, immunofluorescence as well as flow cytometry were performed in vitro or in vivo to determine the effects of Polyporus umbellatus on the progression of human laryngeal cancer. First, the breast cancer cell growth, invasion and migration were inhibited, as well as the tumor volume in nude mice was down-regulated for Polyporus umbellatus use. Additionally, our data also showed that Polyporus umbellatus suppressed breast cancer cells proliferation, which was linked with the down-regulation of AKT activation by Polyporus umbellatus treatment. Mdm was inactivated while p53 was stimulated for Polyporus umbellatus administration, displaying inhibitory role in tumor growth. Furthermore, Polyporus umbellatus could up-regulate breast cancer cells in G0/G1 phase during cell cycle, and at the same time reducing cells in S phase. Also, flow cytometry and western blot assays suggested that apoptosis was induced by the administration of Polyporus umbellatus, which enhanced Caspase-3 expressions by AKT-regulated anti-apoptotic and pro-apoptotic signals. In conclusion, our data indicated that Polyporus umbellatus had a potential role in controlling human breast cancer through inhibiting tumor cell proliferation, inducing apoptosis regulated by AKT, which might provide a therapeutic strategy for breast cancer suppression in the future.