Traditional Chinese Medicine CFF‐1 induced cell growth inhibition, autophagy, and apoptosis via inhibiting EGFR‐related pathways in prostate cancer

• Published in: Cancer medicine (Malden, MA) MA), 2018-04, Vol.7 (4), p.1546-1559
• Main Authors: Wu, Zhaomeng, Zhu, Qingyi, Yin, Yingying, Kang, Dan, Cao, Runyi, Tian, Qian, Zhang, Yu, Lu, Shan, Liu, Ping
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Animals; Antineoplastic Agents, Phytogenic - pharmacology; Apoptosis; Apoptosis - drug effects; Autophagy; Autophagy - drug effects; Biomarkers; Cancer Prevention; Cell cycle; Cell Cycle Checkpoints - drug effects; Cell death; Cell growth; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; CFF‐1; Chinese medicine; Disease Models, Animal; Drugs, Chinese Herbal - pharmacology; EGFR; Epidermal growth factor receptors; Forkhead Box Protein O1 - metabolism; FOXO1 protein; G1 phase; Humans; Male; Medicine, Chinese Traditional; Mice; Original Research; Phagocytosis; Phosphatidylinositol 3-Kinases - metabolism; Phosphorylation; PI3K/AKT signal pathway; Prostate cancer; Prostate cancer (PCa); Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Proto-Oncogene Proteins c-akt - metabolism; Raf protein; Signal Transduction - drug effects; TOR protein; Traditional Chinese medicine; Tumor cell lines; Tumor Suppressor Protein p53 - metabolism; Xenograft Model Antitumor Assays; Xenografts
• ISSN: 2045-7634; 2045-7634
• DOI: 10.1002/cam4.1419

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 (PCa) 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 PI3K/AKT and Raf/Erk signal pathways, resulted in the decrease of p‐FOXO1 (Ser256) and regulated the expression of apoptosis‐related and cycle‐related genes. Moreover, CFF‐1 markedly induced cell autophagy through inhibiting PI3K/AKT/mTOR pathway and then up‐regulating Beclin‐1 and LC‐3II 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 PCa cell growth inhibition, autophagy, and apoptosis suggested that CFF‐1 had the clinical potential to treat patients with prostate cancer. Our study here demonstrated for the first time that Traditional Chinese Medicine CFF‐1 selectively induced prostate cancer cell growth inhibition, autophagy, and apoptosis by competitively targeting EGFR with EGF and then inhibited EGFR‐related signal pathways in vitro and in vivo.