title: Flavokawain B induced cytotoxicity in two breast cancer cell lines, MCF-7 and MDA-MB231 and inhibited the metastatic potential of MDA-MB231 via the regulation of several tyrosine kinases In vitro.
abstract: BACKGROUND
  The kava-kava plant (Piper methysticum) is traditionally consumed by the pacific islanders and has been linked to be involved in several biological activities. Flavokawain B is a unique chalcone, which can be found in the roots of the kava-kava plant. In this study, the operational mechanism of the anti-cancer activity of a synthetic Flavokawain B (FKB) on two breast cancer cell lines, MCF-7 and MDA-MB231 was investigated.
  
  
  METHODS
  Several in vitro assays were attempted such as MTT, flow cytometry of cell cycle analysis, annexin V analysis, and JC-1 analysis to detect apoptosis. Moreover, in vitro metastasis assays were also performed such as transwell migration assay, invasion assay, rat aorta ring and HUVEC tube formation. Molecular analysis of related genes and proteins were conducted using real-time PCR and proteome profiler analysis.
  
  
  RESULTS
  Based on our results, apoptosis was induced when both MCF-7 and MDA-MB231 were treated with FKB. A significant G2/M arrest was seen in MDA-MB231 cells. Additionally, FKB also inhibited the in vitro migration and invasion in MDA-MB231 cells in a dose dependent manner. Moreover, FKB can be a potential inhibitor in angiogenesis as it suppressed the formation of vessels in HUVEC cells as well as in the ex-vivo rat aortic ring assay.
  
  
  CONCLUSIONS
  Our findings suggested that FKB also regulated several receptor tyrosine kinases. Overall, FKB is not only a potential candidate to be an anti-cancer agent, but as an anti-metastatic agent as well.
authors.affiliation: Bright Sparks Unit, Universiti Malaya, 50603, Kuala Lumpur, Malaysia. nadyaboo@gmail.com.|Faculty of Biotechnology and Bimolecular Sciences, Universiti Putra Malaysia, UPM Serdang 43400, Selangor, Darul Ehsan, Malaysia. nadyaboo@gmail.com.
authors.forename: Nadiah
authors.initials: N
authors.lastname: Abu
authors.affiliation: Faculty of Industrial Sciences & Technology, Universiti Malaysia Pahang, Lebuhraya Tun Razak 26300, Kuantan, Pahang, Malaysia. nadeemupm@gmail.com.
authors.forename: M Nadeem
authors.initials: MN
authors.lastname: Akhtar
authors.affiliation: Institute of Bioscience, Universiti Putra Malaysia, UPM Serdang 43400, Selangor, Darul Ehsan, Malaysia. sky2005@gmail.com.
authors.forename: Swee Keong
authors.initials: SK
authors.lastname: Yeap
authors.affiliation: Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Lot PT 21144, Jalan Sungai Long, Bandar Sungai Long, Cheras, 43000, Selangor, Malaysia. promelkl@gmail.com.
authors.forename: Kian Lam
authors.initials: KL
authors.lastname: Lim
authors.affiliation: School of Biomedical Sciences, University of Nottingham Malaysia Campus, Jalan Broga, Semenyih 43500, Selangor, Malaysia. wanyong.ho@nottingham.edu.my.
authors.forename: Wan Yong
authors.initials: WY
authors.lastname: Ho
authors.affiliation: Faculty of Biotechnology and Bimolecular Sciences, Universiti Putra Malaysia, UPM Serdang 43400, Selangor, Darul Ehsan, Malaysia. puad@upm.edu.my.
authors.forename: Mohd Puad
authors.initials: MP
authors.lastname: Abdullah
authors.affiliation: Faculty of Biotechnology and Bimolecular Sciences, Universiti Putra Malaysia, UPM Serdang 43400, Selangor, Darul Ehsan, Malaysia. clho@upm.edu.my.
authors.forename: Chai Ling
authors.initials: CL
authors.lastname: Ho
authors.affiliation: Institute of Bioscience, Universiti Putra Malaysia, UPM Serdang 43400, Selangor, Darul Ehsan, Malaysia. aro@upm.edu.my.
authors.forename: Abdul Rahman
authors.initials: AR
authors.lastname: Omar
authors.affiliation: Faculty of Industrial Sciences & Technology, Universiti Malaysia Pahang, Lebuhraya Tun Razak 26300, Kuantan, Pahang, Malaysia. jamilismail@ump.edu.my.
authors.forename: Jamil
authors.initials: J
authors.lastname: Ismail
authors.affiliation: Faculty of Biotechnology and Bimolecular Sciences, Universiti Putra Malaysia, UPM Serdang 43400, Selangor, Darul Ehsan, Malaysia. noorjahan@upm.edu.my.
authors.forename: Noorjahan Banu
authors.initials: NB
authors.lastname: Alitheen
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D005419:Flavonoids / Q000494:pharmacology / Q000627:therapeutic use*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D020901:Kava / Q000737:chemistry*; D061986:MCF-7 Cells; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D051381:Rats
chemical_list: D020533:Angiogenesis Inhibitors; D000972:Antineoplastic Agents, Phytogenic; D005419:Flavonoids; D010936:Plant Extracts; C452039:flavokawain B; D011505:Protein-Tyrosine Kinases