title: The anti-tumor effect and bioactive phytochemicals of Hedyotis diffusa willd on ovarian cancer cells.
abstract: BACKGROUND
  Hedyotis diffusa willd (HDW) is a widely used medicinal herb in China. It processed various medicinal properties including antioxidative, anti-inflamatory and anti-cancer effects. This study aimed to investigate the anti-tumor effects of HDW on ovarian cancer cells and the underlying mechanisms as well as identify the bioactive compounds.
  
  
  METHODS
  Effects of HDW on the viability of ovarian cancer A2780 cells were detected by MTT assay. Apoptosis was detected by cell morphologic observation through DAPI staining and flow cytometry analysis. The migration of ovarian cancer cells which exposed to HDW were detected by wound healing and transwell assays. The protein levels of caspase 3/9, Bcl-2 and MMP-2/9 in human ovarian cancer cells treated with HDW were assessed by western blotting analysis. The potential bioactive compounds were characterized by HPLC-Q-TOF-MS.
  
  
  RESULTS
  HDW significantly inhibited the growth of A2780 ovarian cancer cells and induced apoptosis. The induction of apoptosis by HDW was associated with down-regulation of anti-apoptotic protein Bcl-2 and the activation of caspase 3/9. Wound healing and transwell chamber assays indicated HDW suppressed the migration of ovarian cancer cells. HDW dramatically decreased MMP-2/9 expression. A HPLC-Q-TOF-MS analysis of HDW indicated the presence of 13 flavonoids compounds and one anthraquinone compound, which may contribute to the anticancer activity of the HDW.
  
  
  CONCLUSIONS
  HDW effectively restricted the growth of ovarian cancer cells and induced apoptosis through the mitochondria-associated apoptotic pathway. Furthermore, HDW suppressed the migration of ovarian cancer cells through down-regulation of MMP-2 and MMP-9 expression. These results showed that HDW hold potential therapeutic effect for ovarian cancer patients.
authors.affiliation: Academy of Integrative Medicine, Dalian Medical University, Dalian 116044, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Biotechnology, Dalian Medical University, Dalian 116044, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Acute Abdomen Department of the First Affiliated Hospital, Dalian medical University, Dalian 116000, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Qi
authors.affiliation: Department of Biotechnology, Dalian Medical University, Dalian 116044, China.
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Jiang
authors.affiliation: Department of Biotechnology, Dalian Medical University, Dalian 116044, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Biotechnology, Dalian Medical University, Dalian 116044, China.
authors.forename: Pei
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Academy of Integrative Medicine, Dalian Medical University, Dalian 116044, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Biotechnology, Dalian Medical University, Dalian 116044, China. Electronic address: liweiling2004@163.com.
authors.forename: Weiling
authors.initials: W
authors.lastname: Li
mesh_terms: D000880:Anthraquinones / Q000302:isolation & purification / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D005260:Female; D005419:Flavonoids / Q000302:isolation & purification / Q000494:pharmacology; D032064:Hedyotis / Q000737:chemistry*; D006801:Humans; D013058:Mass Spectrometry; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009361:Neoplasm Invasiveness; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D064209:Phytochemicals / Q000302:isolation & purification / Q000494:pharmacology*; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal
chemical_list: D000880:Anthraquinones; D000972:Antineoplastic Agents, Phytogenic; D051017:Apoptosis Regulatory Proteins; D005419:Flavonoids; D064209:Phytochemicals; D010936:Plant Extracts; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: Apoptosis; Bioactive phytochemicals; Hedyotis diffusa willd; Migration; Ovarian cancer