Affiliations 

  • 1 Bright Sparks Unit, Universiti Malaya, Kuala Lumpur, Malaysia; Faculty of Biotechnology and Bimolecular Sciences, Universiti Putra Malaysia, Serdang, Selangor Darul Ehsan, Malaysia
  • 2 Faculty of Industrial Sciences & Technology, Universiti Malaysia Pahang, Kuantan, Pahang, Malaysia
  • 3 Institute of Bioscience, Universiti Putra Malaysia, Serdang, Selangor Darul Ehsan, Malaysia
  • 4 Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Cheras, Selangor, Malaysia
  • 5 School of Biomedical Sciences, University of Nottingham Malaysia Campus, Semenyih, Selangor, Malaysia
  • 6 Faculty of Biotechnology and Bimolecular Sciences, Universiti Putra Malaysia, Serdang, Selangor Darul Ehsan, Malaysia
  • 7 Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor Darul Ehsan, Malaysia
PLoS One, 2014;9(10):e105244.
PMID: 25286005 DOI: 10.1371/journal.pone.0105244

Abstract

INTRODUCTION: 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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.