PMID- 27367669 OWN - NLM STAT- MEDLINE DCOM- 20170321 LR - 20181113 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 17 IP - 7 DP - 2016 Jun 28 TI - A Homogeneous Polysaccharide from Fructus Schisandra chinensis (Turz.) Baill Induces Mitochondrial Apoptosis through the Hsp90/AKT Signalling Pathway in HepG2 Cells. LID - 10.3390/ijms17071015 [doi] LID - 1015 AB - According to the potential anti-hepatoma therapeutic effect of Schisandra chinensis polysaccharides presented in previous studies, a bioactive constituent, homogeneous Schisandra chinensis polysaccharide-0-1 (SCP-0-1), molecular weight (MW) circa 69.980 kDa, was isolated and purified. We assessed the efficacy of SCP-0-1 against human hepatocellular liver carcinoma (HepG2) cells to investigate the effects of its antitumour activity and molecular mechanisms. Anticancer activity was evaluated using microscopy, 3-[4,5-dimethyl-2-thiazolyl]-2,5-diphenyltetrazolium bromide (MTT) assay, Hoechst 33258 staining, acridine orange (AO) staining, flow cytometry (FCM), and cell-cycle analysis. SCP-0-1 inhibited the HepG2 cells' growth via inducing apoptosis and second gap/mitosis (G2/M) arrest dose-dependently, with a half maximal inhibitory concentration (IC50) value of 479.63 microg/mL. Western blotting of key proteins revealed the apoptotic and autophagic potential of SCP-0-1. Besides, SCP-0-1 upregulated Bcl-2 Associated X Protein (Bax) and downregulated B-cell leukemia/lymphoma 2 (Bcl-2) in the HepG2 cells. The expression of caspase-3, -8, and -9; poly (ADP-ribose) polymerase (PARP); cytochrome c (Cyt C); tumor protein 53 (p53); survivin; sequestosome 1 (p62); microtubule-associated protein 1 light chain-3B (LC3B); mitogen-activated protein kinase p38 (p38); extracellular regulated protein kinases (ERK); c-Jun N-terminal kinase (JNK); protein kinase B (AKT); and heat shock protein 90 (Hsp90) were evaluated using Western blotting. Our findings demonstrate a novel mechanism through which SCP-0-1 exerts its antiproliferative activity and induces mitochondrial apoptosis rather than autophagy. The induction of mitochondrial apoptosis was attributed to the inhibition of the Hsp90/AKT signalling pathway in an extracellular signal-regulated kinase-independent manner. The results also provide initial evidence on a molecular basis that SCP-0-1 can be used as an anti-hepatocellular carcinoma therapeutic agent in the future. FAU - Chen, Yonglin AU - Chen Y AD - The MOE Key Laboratory for Standardization of Chinese Medicines, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. syxcyl@foxmail.com. AD - The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. syxcyl@foxmail.com. AD - Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. syxcyl@foxmail.com. FAU - Shi, Songshan AU - Shi S AD - The MOE Key Laboratory for Standardization of Chinese Medicines, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. shisongshan1978@126.com. AD - The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. shisongshan1978@126.com. AD - Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. shisongshan1978@126.com. FAU - Wang, Huijun AU - Wang H AD - The MOE Key Laboratory for Standardization of Chinese Medicines, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. wanghuijun666666@163.com. AD - The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. wanghuijun666666@163.com. AD - Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. wanghuijun666666@163.com. FAU - Li, Ning AU - Li N AD - The MOE Key Laboratory for Standardization of Chinese Medicines, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. miss1991lining@163.com. AD - The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. miss1991lining@163.com. AD - Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. miss1991lining@163.com. FAU - Su, Juan AU - Su J AD - The MOE Key Laboratory for Standardization of Chinese Medicines, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. ssujuan77@163.com. AD - The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. ssujuan77@163.com. AD - Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. ssujuan77@163.com. FAU - Chou, Guixin AU - Chou G AD - The MOE Key Laboratory for Standardization of Chinese Medicines, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. chouguixinzyb@126.com. AD - The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. chouguixinzyb@126.com. AD - Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. chouguixinzyb@126.com. FAU - Wang, Shunchun AU - Wang S AD - The MOE Key Laboratory for Standardization of Chinese Medicines, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. shunchunwang@126.com. AD - The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. shunchunwang@126.com. AD - Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. shunchunwang@126.com. LA - eng PT - Journal Article DEP - 20160628 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (HSP90 Heat-Shock Proteins) RN - 0 (P62 protein, human) RN - 0 (Polysaccharides) RN - 0 (RNA-Binding Proteins) RN - 0 (TP53 protein, human) RN - 0 (Tumor Suppressor Protein p53) RN - 0 (bcl-2-Associated X Protein) RN - 9007-43-6 (Cytochromes c) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) RN - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) SB - IM MH - Apoptosis/drug effects MH - Cytochromes c/metabolism MH - Extracellular Signal-Regulated MAP Kinases/metabolism MH - HSP90 Heat-Shock Proteins/*metabolism MH - Hep G2 Cells MH - Humans MH - JNK Mitogen-Activated Protein Kinases/metabolism MH - Mitochondria/drug effects MH - Polysaccharides/*pharmacology MH - Proto-Oncogene Proteins c-akt/*metabolism MH - RNA-Binding Proteins/metabolism MH - Schisandra/*chemistry MH - Tumor Suppressor Protein p53/metabolism MH - bcl-2-Associated X Protein/metabolism MH - p38 Mitogen-Activated Protein Kinases/metabolism PMC - PMC4964391 OTO - NOTNLM OT - Hsp90/AKT signalling pathway OT - Schisandra chinensis OT - autophagy OT - hepatocellular carcinoma OT - mitochondrial apoptosis OT - polysaccharide EDAT- 2016/07/02 06:00 MHDA- 2017/03/23 06:00 PMCR- 2016/07/01 CRDT- 2016/07/02 06:00 PHST- 2016/04/14 00:00 [received] PHST- 2016/06/10 00:00 [revised] PHST- 2016/06/17 00:00 [accepted] PHST- 2016/07/02 06:00 [entrez] PHST- 2016/07/02 06:00 [pubmed] PHST- 2017/03/23 06:00 [medline] PHST- 2016/07/01 00:00 [pmc-release] AID - ijms17071015 [pii] AID - ijms-17-01015 [pii] AID - 10.3390/ijms17071015 [doi] PST - epublish SO - Int J Mol Sci. 2016 Jun 28;17(7):1015. doi: 10.3390/ijms17071015.