title: Mechanisms of action of 17βH-neriifolin on its anticancer effect in SKOV-3 ovarian cancer cell line.
abstract: OBJECTIVE
  Abnormalities in apoptotic signalling pathways often occur in cancer cells and limit the successful chemotherapy outcomes in cancers. Therefore, there is an urgent need to discover new anticancer agents with novel mechanisms of action to overcome the resistance effect in chemotherapy.
  
  
  METHODS
  In the present study, the anticancer effects and the mechanisms of action of 17βH-neriifolin (cardiac glycoside) were evaluated by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay and a proteomic approach in treated and non-treated SKOV-3 ovarian cancer cells.
  
  
  RESULTS
  17βH-neriifolin was found to be active with IC50 values of 0.01 ± 0.001 in SKOV-3 ovarian cancer cell line, as evaluated by the sulforhodamine B (SRB) assay. RESULTS from TUNEL assay indicated that 17βH-neriifolin caused apoptosis in SKOV-3 cells in a dose-dependent manner. Based on differential analysis of treated and non-treated SKOV-3 two-dimensional electrophoresis (2-DE) profiles, four proteins, namely vimentin (VIM), pyruvate kinase, muscle (PKM), heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) and transgelin (TAGLN1) were identified to be involved in apoptosis. Other proteins including piggybac transposable element derived 5 (PGBD5), DENN/MADD domain containing 2D (DENND2D) and formin-like 1(FMNL) have also been identified to be associated in SKOV-3 cell death induced by 17βH-neriifolin.
  
  
  CONCLUSIONS
  These findings may provide new insights on the potential of 17βH-neriifolin's mechanism of action in killing ovarian cancer cells.
authors: Natural Products Division, Forest Research Institute Malaysia, Kepong, Selangor, Malaysia syarifah@frim.gov.my.
authors: Siti-Syarifah Mohd
authors: SS
authors: Mutalip
authors: Natural Products Division, Forest Research Institute Malaysia, Kepong, Selangor, Malaysia.
authors: Nurhanan Murni
authors: NM
authors: Yunos
authors: Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia University of Malaya Centre for Proteomic Research, University of Malaya, Kuala Lumpur, Malaysia.
authors: Puteri Shafinaz Akmar
authors: PS
authors: Abdul-Rahman
authors: Natural Products Division, Forest Research Institute Malaysia, Kepong, Selangor, Malaysia.
authors: Muhammad Haffiz
authors: MH
authors: Jauri
authors: Natural Products Division, Forest Research Institute Malaysia, Kepong, Selangor, Malaysia.
authors: Asiah
authors: A
authors: Osman
authors: Natural Products Division, Forest Research Institute Malaysia, Kepong, Selangor, Malaysia.
authors: Mohd Ilham
authors: MI
authors: Adenan
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002298:Cardenolides / Q000494:pharmacology*; D002352:Carrier Proteins / Q000502:physiology; D045744:Cell Line, Tumor; D005260:Female; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B / Q000502:physiology; D006801:Humans; D008565:Membrane Proteins / Q000502:physiology; D008840:Microfilament Proteins / Q000502:physiology; D009124:Muscle Proteins / Q000502:physiology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013963:Thyroid Hormones / Q000502:physiology; D000097810:Thyroid Hormone-Binding Proteins
chemical_list: D000970:Antineoplastic Agents; D002298:Cardenolides; D002352:Carrier Proteins; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D008565:Membrane Proteins; D008840:Microfilament Proteins; D009124:Muscle Proteins; D013963:Thyroid Hormones; D000097810:Thyroid Hormone-Binding Proteins; C000619656:hnRNPA1 protein, human; C051615:transgelin; C040684:neriifolin
keywords: Cardiac glycosides; anticancer; apoptosis; ovarian cancer; proteomics