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Flavokawain A induces apoptosis in MCF-7 and MDA-MB231 and inhibits the metastatic process in vitro

Abu, Nadiah and Akhtar, Muhammad Nadeem and Yeap, Swee Keong and Lim, Kian Lam and Ho, Wan Yong and Zulfadli, Aimi Jamil and Omar, Abdul Rahman and Sulaiman, Mohd Roslan and Abdullah, Mohd Puad and Mohamed Alitheen, Noorjahan Banu (2014) Flavokawain A induces apoptosis in MCF-7 and MDA-MB231 and inhibits the metastatic process in vitro. PLOS ONE, 9 (10). art. no. e105244. pp. 1-12. ISSN 1932-6203

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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.

Item Type:Article
Keyword:Anti-cancer drug; Metastatic process; Flavokawain A; FKA
Faculty or Institute:Faculty of Biotechnology and Biomolecular Sciences
Faculty of Medicine and Health Science
Institute of Bioscience
Publisher:Public Library of Science
DOI Number:10.1371/journal.pone.0105244
Altmetrics:http://www.altmetric.com/details.php?domain=psasir.upm.edu.my&doi=10.1371/journal.pone.0105244
ID Code:37683
Deposited By: Nabilah Mustapa
Deposited On:18 Dec 2015 10:21
Last Modified:18 Dec 2015 10:21

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