Isorhapontigenin induced cell growth inhibition and apoptosis by targeting EGFR-related pathways in prostate cancer.

Isorhapontigenin (ISO), a naturally phytopolyphenol compound existing in Chinese herb, apples, and various vegetables, has attracted extensive interest in recent years for its diverse pharmacological characteristics. Increasing evidences reveal that ISO can inhibit cancer cell growth by induced apoptosis, however, the molecular mechanisms is not fully understood. In this study, we found for the first time that ISO apparently induced cell growth inhibition and apoptosis by targeting EGFR and its downstream signal pathways in prostate cancer (PCa) cells both in vitro and in vivo, whereas no obviously effect on normal prostate cells. From the results, we found that ISO competitively targeted EGFR with EGF and inhibited EGFR auto-phosphorylation, and then decreased the levels of p-Erk1/2, p-PI3 K, and p-AKT, and further induced down-regulation of p-FOXO1 and promoted FOXO1 nuclear translocation; and finally resulted in a significantly up-regulation of Bim/p21/27/Bax/cleaved Caspase-3/cleaved PARP-1 and a markedly down-regulation of Sp1/Bcl-2/XIAP/Cyclin D1. Moreover, our experimental data demonstrated that treatment of ISO decreased protein level of AR via both inhibiting the expression of AR gene and promoting the ubiquitination/degradation of AR proteins in proteasome. In vivo, we also found that ISO inhibited the growth of subcutaneous xenotransplanted tumor in nude mice by inducing PCa cell growth inhibition and apoptosis. Taken together, all findings here clearly implicated that EGFR-related signal pathways, including EGFR-PI3K-Akt and EGFR-Erk1/2 pathways, were involved in ISO-induced cell growth inhibition and apoptosis in PCa cells, providing a more solid theoretical basis for the application of ISO to treat patients with prostate cancer in clinic.

Zhu C ，Zhu Q ，Wu Z ，Yin Y ，Kang D ，Lu S ，Liu P ... -  《-》

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

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.

Wu Z ，Zhu Q ，Yin Y ，Kang D ，Cao R ，Tian Q ，Zhang Y ，Lu S ，Liu P ... -  《-》

Tanshinones from Chinese medicinal herb Danshen (Salvia miltiorrhiza Bunge) suppress prostate cancer growth and androgen receptor signaling.

Zhang Y ，Won SH ，Jiang C ，Lee HJ ，Jeong SJ ，Lee EO ，Zhang J ，Ye M ，Kim SH ，Lü J ... -  《-》

EGFR‑associated pathways involved in traditional Chinese medicine (TCM)‑1‑induced cell growth inhibition, autophagy and apoptosis in prostate cancer.

Wu Z ，Zhu Q ，Zhang Y ，Yin Y ，Kang D ，Cao R ，Tian Q ，Lu S ，Liu P ... -  《-》

Goserelin promotes the apoptosis of epithelial ovarian cancer cells by upregulating forkhead box O1 through the PI3K/AKT signaling pathway.

Zhang N ，Qiu J ，Zheng T ，Zhang X ，Hua K ，Zhang Y ... -  《-》