title: Pogostone induces autophagy and apoptosis involving PI3K/Akt/mTOR axis in human colorectal carcinoma HCT116 cells.
abstract: BACKGROUND
  Pogostemon cablin is a medicinal herb widely used to treat gastrointestinal diseases in many Asian countries. Pogostone is an important constituent of Pogostemon cablin, and possesses various bioactivitys. In this study, we performed to investigate the anti-colorectal tumor property of Pogostone by inducing aurophagy and apoptosis in human colorectal cancer cells, and to define the potential molecular mechanisms.
  
  
  METHODS
  In vitro, The anti-tumor activity of pogostone was assessed using MTT assay. Autophagy was monitored by transmission electron microscopy observation and mRFP-GFP-LC3 fluorescence analysis in colorectal tumor cell line. Apoptosis was measured by flow cytometry and annexinV-FITC/PI staining. The protein expressions or activition of LC3-Ⅱ, AKT, mTOR, caspase-3 and caspase-7 were detected through western blotting. In vivo, the anti-tumor effect of pogostone was tested with HCT116 colorectal tumor cells transplantation tumor model. The expression of Ki-67 was determined by Immunohistochemistry staining and the apoptosis was evaluated using TUNEL assay.
  
  
  RESULTS
  In vitro, pogostone exhibits significant anti-tumor activity against human cancer cell lines, especially for HCT116 (18.7±1.93μg/ml). Transmission electron microscopy observation, mRFP-GFP-LC3 fluorescence analysis, flow cytometry and assay and western blotting detection revealed that the anti-colorectal tumor activity of pogostone was dependent on inducing autophagy and apoptosis through up-regulating the expression of LC3-Ⅱ, cleaved caspase-7 and caspase-3, and decreasing the phosphorylation of AKT/mTOR. In vivo, 150mg/kg pogostone inhibited the HCT116 tumor growth in immunodeficient mice with an inhibitory rate of 43.3%, decreased the expression of Ki67, and induced apoptosis in three days.
  
  
  CONCLUSIONS
  Pogostone showed anti-colorectal tumor effects by inducing autophagy and apoptosis involving PI3K/Akt/mTOR axis. Thus, pogostone may be a promising lead compound to be further developed for cancer therapy.
authors.affiliation: Pharmacy College, Chengdu University of Traditional Chinese Medicine, The Ministry of Education Key Laboratory of Standardization of Chinese Herbal Medicine, Key Laboratory of Systematic Research, Development and Utilization of Chinese Medicine Resources in Sichuan Province, Key Laboratory Breeding Base of Co-founded by Sichuan Province and MOST, PR China.
authors.forename: Zhi-Xing
authors.initials: ZX
authors.lastname: Cao
authors.affiliation: Pharmacy College, Chengdu University of Traditional Chinese Medicine, The Ministry of Education Key Laboratory of Standardization of Chinese Herbal Medicine, Key Laboratory of Systematic Research, Development and Utilization of Chinese Medicine Resources in Sichuan Province, Key Laboratory Breeding Base of Co-founded by Sichuan Province and MOST, PR China.
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Yang
authors.affiliation: Pharmacy College, Chengdu University of Traditional Chinese Medicine, The Ministry of Education Key Laboratory of Standardization of Chinese Herbal Medicine, Key Laboratory of Systematic Research, Development and Utilization of Chinese Medicine Resources in Sichuan Province, Key Laboratory Breeding Base of Co-founded by Sichuan Province and MOST, PR China.
authors.forename: Si
authors.initials: S
authors.lastname: Yu
authors.affiliation: Pharmacy College, Chengdu University of Traditional Chinese Medicine, The Ministry of Education Key Laboratory of Standardization of Chinese Herbal Medicine, Key Laboratory of Systematic Research, Development and Utilization of Chinese Medicine Resources in Sichuan Province, Key Laboratory Breeding Base of Co-founded by Sichuan Province and MOST, PR China.
authors.forename: Yu-Zhi
authors.initials: YZ
authors.lastname: Li
authors.affiliation: Pharmacy College, Chengdu University of Traditional Chinese Medicine, The Ministry of Education Key Laboratory of Standardization of Chinese Herbal Medicine, Key Laboratory of Systematic Research, Development and Utilization of Chinese Medicine Resources in Sichuan Province, Key Laboratory Breeding Base of Co-founded by Sichuan Province and MOST, PR China; School of Medical Technology, Chengdu University of Traditional Chinese Medicine, PR China.
authors.forename: Wen-Wen
authors.initials: WW
authors.lastname: Wang
authors.affiliation: Pharmacy College, Chengdu University of Traditional Chinese Medicine, The Ministry of Education Key Laboratory of Standardization of Chinese Herbal Medicine, Key Laboratory of Systematic Research, Development and Utilization of Chinese Medicine Resources in Sichuan Province, Key Laboratory Breeding Base of Co-founded by Sichuan Province and MOST, PR China; School of Medical Technology, Chengdu University of Traditional Chinese Medicine, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Huang
authors.affiliation: Pharmacy College, Chengdu University of Traditional Chinese Medicine, The Ministry of Education Key Laboratory of Standardization of Chinese Herbal Medicine, Key Laboratory of Systematic Research, Development and Utilization of Chinese Medicine Resources in Sichuan Province, Key Laboratory Breeding Base of Co-founded by Sichuan Province and MOST, PR China.
authors.forename: Xiao-Fang
authors.initials: XF
authors.lastname: Xie
authors.affiliation: Pharmacy College, Chengdu University of Traditional Chinese Medicine, The Ministry of Education Key Laboratory of Standardization of Chinese Herbal Medicine, Key Laboratory of Systematic Research, Development and Utilization of Chinese Medicine Resources in Sichuan Province, Key Laboratory Breeding Base of Co-founded by Sichuan Province and MOST, PR China.
authors.forename: Liang
authors.initials: L
authors.lastname: Xiong
authors.affiliation: Department of pathology, West China Hospital, PR China.
authors.forename: Song
authors.initials: S
authors.lastname: Lei
authors.affiliation: Pharmacy College, Chengdu University of Traditional Chinese Medicine, The Ministry of Education Key Laboratory of Standardization of Chinese Herbal Medicine, Key Laboratory of Systematic Research, Development and Utilization of Chinese Medicine Resources in Sichuan Province, Key Laboratory Breeding Base of Co-founded by Sichuan Province and MOST, PR China. Electronic address: pengchengchengdu@126.com.
authors.forename: Cheng
authors.initials: C
authors.lastname: Peng
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D015179:Colorectal Neoplasms; D005260:Female; D045325:HCT116 Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009822:Oils, Volatile / Q000494:pharmacology*; D051058:Oncogene Protein v-akt / Q000187:drug effects; D019869:Phosphatidylinositol 3-Kinases / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D009822:Oils, Volatile; D051058:Oncogene Protein v-akt; D019869:Phosphatidylinositol 3-Kinases; D058570:TOR Serine-Threonine Kinases; C483658:Pogostone; C546842:MTOR protein, human
keywords: Akt; Apoptosis; Autophagy; Pogostone; mTOR