Open AccessTraditional Chinese Medicine CFF ‐1 induced cell growth inhibition, autophagy, and apoptosis via inhibiting EGFR ‐related pathways in prostate cancer
Author(s) -
Wu Zhaomeng,
Zhu Qingyi,
Yin Yingying,
Kang Dan,
Cao Runyi,
Tian Qian,
Zhang Yu,
Lu Shan,
Liu Ping
Publication year - 2018
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.1419
Subject(s) - apoptosis , pi3k/akt/mtor pathway , protein kinase b , autophagy , cell cycle , mapk/erk pathway , cancer research , cell growth , prostate cancer , in vivo , cell cycle checkpoint , chemistry , signal transduction , cancer , pharmacology , medicine , biology , biochemistry , microbiology and biotechnology
Traditional Chinese medicine ( TCM ) has a combined therapeutic result in cancer treatment by integrating holistic and local therapeutical effects, by which TCM can enhance the curative effect and reduce the side effect. In this study, we analyzed the effect of CFF ‐1 (alcohol extract from an anticancer compound Chinese medicine) on prostate cancer ( PC a) cell lines and studied in detail the mechanism of cell death induced by CFF ‐1 in vitro and in vivo. From our data, we found for the first time that CFF ‐1 obviously arrested cell cycle in G1 phase, decreased cell viability and then increased nuclear rupture in a dose‐dependent manner and finally resulted in apoptosis in prostate cancer cells. In molecular level, our data showed that CFF ‐1 induced inhibition of EGFR auto‐phosphorylation and inactivation of EGFR . Disruption of EGFR activity in turn suppressed downstream PI 3K/ AKT and Raf/Erk signal pathways, resulted in the decrease of p‐ FOXO 1 (Ser256) and regulated the expression of apoptosis‐related and cycle‐related genes. Moreover, CFF ‐1 markedly induced cell autophagy through inhibiting PI 3K/ AKT / mTOR pathway and then up‐regulating Beclin‐1 and LC ‐3 II and down‐regulating phosphorylation of p70S6K. In vivo, CFF ‐1‐treated group exhibited a significant decrease in tumor volume compared with the negative control group in subcutaneous xenograft tumor in nude mice via inhibiting EGFR ‐related signal pathways. Thus, bio‐functions of Chinese medicine CFF ‐1 in inducing PC a cell growth inhibition, autophagy, and apoptosis suggested that CFF ‐1 had the clinical potential to treat patients with prostate cancer.