title: Flavokawain A induces apoptosis in MCF-7 and MDA-MB231 and inhibits the metastatic process in vitro.
abstract: BACKGROUND
  The kava-kava plant (Piper methsyticum) is traditionally known as the pacific elixir by the pacific islanders for its role in a wide range of biological activities. The extract of the roots of this plant contains a variety of interesting molecules including Flavokawain A and this molecule is known to have anti-cancer properties. Breast cancer is still one of the leading diagnosed cancers in women today. The metastatic process is also very pertinent in the progression of tumorigenesis.
  
  
  METHODS
  MCF-7 and MDA-MB231 cells were treated with several concentrations of FKA. The apoptotic analysis was done through the MTT assay, BrdU assay, Annexin V analysis, cell cycle analysis, JC-1 mitochondrial dye, AO/PI dual staining, caspase 8/9 fluorometric assay, quantitative real time PCR and western blot. For the metastatic assays, the in vitro scratch assay, trans-well migration/invasion assay, HUVEC tube formation assay, ex vivo rat aortic ring assay, quantitative real time PCR and western blot were employed.
  
  
  RESULTS
  We have investigated the effects of FKA on the apoptotic and metastatic process in two breast cancer cell lines. FKA induces apoptosis in both MCF-7 and MDA-MB231 in a dose dependent manner through the intrinsic mitochondrial pathway. Additionally, FKA selectively induces a G2/M arrest in the cell cycle machinery of MDA-MB231 and G1 arrest in MCF-7. This suggests that FKA's anti-cancer activity is dependent on the p53 status. Moreover, FKA also halted the migration and invasion process in MDA-MB231. The similar effects can be seen in the inhibition of the angiogenesis process as well.
  
  
  CONCLUSIONS
  FKA managed to induce apoptosis and inhibit the metastatic process in two breast cancer cell lines, in vitro. Overall, FKA may serve as a promising candidate in the search of a new anti-cancer drug especially in halting the metastatic process but further in vivo evidence is needed.
authors.affiliation: Bright Sparks Unit, Universiti Malaya, Kuala Lumpur, Malaysia; Faculty of Biotechnology and Bimolecular Sciences, Universiti Putra Malaysia, Serdang, Selangor Darul Ehsan, Malaysia.
authors.forename: Nadiah
authors.initials: N
authors.lastname: Abu
authors.affiliation: Faculty of Industrial Sciences & Technology, Universiti Malaysia Pahang, Kuantan, Pahang, Malaysia.
authors.forename: M Nadeem
authors.initials: MN
authors.lastname: Akhtar
authors.affiliation: Institute of Bioscience, Universiti Putra Malaysia, Serdang, Selangor Darul Ehsan, Malaysia.
authors.forename: Swee Keong
authors.initials: SK
authors.lastname: Yeap
authors.affiliation: Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Cheras, Selangor, Malaysia.
authors.forename: Kian Lam
authors.initials: KL
authors.lastname: Lim
authors.affiliation: School of Biomedical Sciences, University of Nottingham Malaysia Campus, Semenyih, Selangor, Malaysia.
authors.forename: Wan Yong
authors.initials: WY
authors.lastname: Ho
authors.affiliation: Faculty of Biotechnology and Bimolecular Sciences, Universiti Putra Malaysia, Serdang, Selangor Darul Ehsan, Malaysia.
authors.forename: Aimi Jamil
authors.initials: AJ
authors.lastname: Zulfadli
authors.affiliation: Institute of Bioscience, Universiti Putra Malaysia, Serdang, Selangor Darul Ehsan, Malaysia.
authors.forename: Abdul Rahman
authors.initials: AR
authors.lastname: Omar
authors.affiliation: Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor Darul Ehsan, Malaysia.
authors.forename: Mohd Roslan
authors.initials: MR
authors.lastname: Sulaiman
authors.affiliation: Faculty of Biotechnology and Bimolecular Sciences, Universiti Putra Malaysia, Serdang, Selangor Darul Ehsan, Malaysia.
authors.forename: Mohd Puad
authors.initials: MP
authors.lastname: Abdullah
authors.affiliation: Faculty of Biotechnology and Bimolecular Sciences, Universiti Putra Malaysia, Serdang, Selangor Darul Ehsan, Malaysia.
authors.forename: Noorjahan Banu
authors.initials: NB
authors.lastname: Alitheen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000098:blood supply / Q000235:genetics / Q000473:pathology*; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002599:Chalcone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D016195:G2 Phase / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D061986:MCF-7 Cells; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008938:Mitosis / Q000187:drug effects; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000473:pathology / Q000517:prevention & control*; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction
chemical_list: C500809:flavokawain A; D002599:Chalcone; D053181:Caspase 8; D053453:Caspase 9