title: A Aconitum coreanum polysaccharide fraction induces apoptosis of hepatocellular carcinoma (HCC) cells via pituitary tumor transforming gene 1 (PTTG1)-mediated suppression of the P13K/Akt and activation of p38 MAPK signaling pathway and displays antitumor activity in vivo.
abstract: In this study, we observed that a Aconitum coreanum polysaccharide (CACP) exhibited an effective inhibitory effect on H22 cell growth in vitro and in vivo via the induction of apoptosis. Further, quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting assays revealed that the expression of pituitary tumor transforming gene 1 (PTTG1), one proto-oncogene, was evidently suppressed in both transcript and protein levels in H22 cell model or mice after CACP treatment. Particularly, CACP (40 μg/ml) treatment or transfection with PTTG1 small interfering RNA (siRNA) could greatly reduce the phosphorylation of Akt (p-Akt) but increase phospho-p38 mitogen-activated protein kinase (p-p38 MARK) protein levels in H22 cells as compared with vehicle-treated cells. Likewise, following treatment of H22-tumor-bearing mice with CACP (100 mg/kg), doxorubicin (DOX, 3 mg/kg), and their combination, tumor tissues showed an attenuated p-Akt protein expression, but a striking p-p38 MARK level when compared with those in model mice. Taken together, we demonstrated here the inhibitory effect of CACP on the growth of H22 cells in vitro and in vivo, which may be through, at least partly, repression of PTTG1 and then followed by the inactivation of P13/Akt and activation of p38 MARK signaling pathways. These findings offered a novel approach for the treatment of hepatocellular carcinoma (HCC) in the future.
authors: Department of Infectious Diseases, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, China. minglianghmu@126.com.
authors: Ming
authors: M
authors: Liang
authors: Department of Infectious Diseases, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, China.
authors: Jianchao
authors: J
authors: Liu
authors: Department of Infectious Diseases, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, China.
authors: Hongyu
authors: H
authors: Ji
authors: Department of Infectious Diseases, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, China.
authors: Moyang
authors: M
authors: Chen
authors: Department of Infectious Diseases, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, China.
authors: Yonghua
authors: Y
authors: Zhao
authors: Department of Infectious Diseases, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, China.
authors: Shuchen
authors: S
authors: Li
authors: Department of Infectious Diseases, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, China.
authors: Xiaoyu
authors: X
authors: Zhang
authors: Department of Infectious Diseases, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, China.
authors: Jingyuan
authors: J
authors: Li
mesh_terms: D031841:Aconitum / Q000737:chemistry; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D058534:Class I Phosphatidylinositol 3-Kinases; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D051379:Mice; D051058:Oncogene Protein v-akt / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D011134:Polysaccharides / Q000008:administration & dosage* / Q000737:chemistry; D000090063:Proto-Oncogene Mas; D064249:Securin / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics*
chemical_list: D058534:Class I Phosphatidylinositol 3-Kinases; D051058:Oncogene Protein v-akt; D019869:Phosphatidylinositol 3-Kinases; D011134:Polysaccharides; D000090063:Proto-Oncogene Mas; D064249:Securin; D048051:p38 Mitogen-Activated Protein Kinases; C000715470:MAS1 protein, human; C578002:pituitary tumor-transforming protein 1, human; C421683:Pik3cd protein, mouse
keywords: Aconitum coreanum; Antitumor; P13K/Akt; Pituitary tumor transforming gene 1 (PTTG1); Polysaccharides; p38 MAPK