Traditional Chinese Medicine CFF-1 induced cell growth inhibition, autophagy, and apoptosis via inhibiting EGFR-related pathways in prostate cancer.
Traditional Chinese Medicine CFF-1 induced cell growth inhibition, autophagy, and apoptosis via inhibiting EGFR-related pathways in prostate cancer.
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DOI：
10.1002/cam4.1419
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发表时间：
2018-04
期刊：
影响因子：
4
通讯作者：
Liu P
中科院分区：
文献类型：
--
作者：
Wu Z;Zhu Q;Yin Y;Kang D;Cao R;Tian Q;Zhang Y;Lu S;Liu P
中医在癌症治疗中具有综合治疗效果，将整体治疗与局部治疗相结合，提高疗效，减少副作用。本研究分析了抗癌复方中药醇提物CFF‐1对前列腺癌（PCa）细胞株的作用，并详细探讨了CFF‐1在体外和体内诱导细胞死亡的机制。从我们的数据中，我们首次发现CFF‐1在前列腺癌细胞的G1期明显阻滞细胞周期，降低细胞活力，然后增加核破裂，并以剂量依赖性的方式最终导致细胞凋亡。在分子水平上，我们的数据显示CFF‐1诱导EGFR自磷酸化抑制和EGFR失活。EGFR活性的破坏反过来抑制下游PI3K/AKT和Raf/Erk信号通路，导致p - fox01 （Ser256）的减少，并调节凋亡相关和周期相关基因的表达。此外，CFF‐1通过抑制PI3K/AKT/mTOR通路，进而上调Beclin‐1和LC‐3II，下调p70S6K的磷酸化水平，显著诱导细胞自噬。在体内，与阴性对照组相比，CFF‐1处理组通过抑制EGFR‐相关信号通路，在裸鼠皮下移植瘤中肿瘤体积显著减少。因此，中药CFF‐1诱导前列腺癌细胞生长抑制、自噬和凋亡的生物学功能提示CFF‐1具有治疗前列腺癌的临床潜力。
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.
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DOI：
10.1016/j.apsb.2015.07.001
发表时间：
2015-09
期刊：
Acta pharmaceutica Sinica. B
影响因子：
--
作者：
Huang L;Fu L
通讯作者：
Fu L
影响因子：
13.3
作者：
Crighton, Diane;Wilkinson, Simon;Ryan, Kevin M.
通讯作者：
Ryan, Kevin M.
影响因子：
8
作者：
Essafi, A;de Mattos, SF;Lam, EWF
通讯作者：
Lam, EWF
影响因子：
45.3
作者：
Burstein, Harold J.;Krilov, Lada;Dizon, Don S.
通讯作者：
Dizon, Don S.
影响因子：
2.7
作者：
Lu, J.;Zhao, H.;Shen, Z.
通讯作者：
Shen, Z.