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

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 molec...

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Main Authors: Abu, Nadiah, Akhtar, Muhammad Nadeem, Yeap, Swee Keong, Lim, Kian Lam, Ho, Wan Yong, Zulfadli, Aimi Jamil, Omar, Abdul Rahman, Sulaiman, Mohd Roslan, Abdullah, Mohd Puad, Mohamed Alitheen, Noorjahan Banu
Format: Article
Language:English
Published: Public Library of Science 2014
Online Access:http://psasir.upm.edu.my/id/eprint/37683/1/37683.pdf
http://psasir.upm.edu.my/id/eprint/37683/
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spelling my.upm.eprints.376832015-12-18T02:21:48Z http://psasir.upm.edu.my/id/eprint/37683/ Flavokawain A induces apoptosis in MCF-7 and MDA-MB231 and inhibits the metastatic process in vitro Abu, Nadiah Akhtar, Muhammad Nadeem Yeap, Swee Keong Lim, Kian Lam Ho, Wan Yong Zulfadli, Aimi Jamil Omar, Abdul Rahman Sulaiman, Mohd Roslan Abdullah, Mohd Puad Mohamed Alitheen, Noorjahan Banu 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. Public Library of Science 2014-10 Article PeerReviewed application/pdf en http://psasir.upm.edu.my/id/eprint/37683/1/37683.pdf 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 10.1371/journal.pone.0105244
institution Universiti Putra Malaysia
building UPM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Putra Malaysia
content_source UPM Institutional Repository
url_provider http://psasir.upm.edu.my/
language English
description 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.
format Article
author Abu, Nadiah
Akhtar, Muhammad Nadeem
Yeap, Swee Keong
Lim, Kian Lam
Ho, Wan Yong
Zulfadli, Aimi Jamil
Omar, Abdul Rahman
Sulaiman, Mohd Roslan
Abdullah, Mohd Puad
Mohamed Alitheen, Noorjahan Banu
spellingShingle Abu, Nadiah
Akhtar, Muhammad Nadeem
Yeap, Swee Keong
Lim, Kian Lam
Ho, Wan Yong
Zulfadli, Aimi Jamil
Omar, Abdul Rahman
Sulaiman, Mohd Roslan
Abdullah, Mohd Puad
Mohamed Alitheen, Noorjahan Banu
Flavokawain A induces apoptosis in MCF-7 and MDA-MB231 and inhibits the metastatic process in vitro
author_facet Abu, Nadiah
Akhtar, Muhammad Nadeem
Yeap, Swee Keong
Lim, Kian Lam
Ho, Wan Yong
Zulfadli, Aimi Jamil
Omar, Abdul Rahman
Sulaiman, Mohd Roslan
Abdullah, Mohd Puad
Mohamed Alitheen, Noorjahan Banu
author_sort Abu, Nadiah
title Flavokawain A induces apoptosis in MCF-7 and MDA-MB231 and inhibits the metastatic process in vitro
title_short Flavokawain A induces apoptosis in MCF-7 and MDA-MB231 and inhibits the metastatic process in vitro
title_full Flavokawain A induces apoptosis in MCF-7 and MDA-MB231 and inhibits the metastatic process in vitro
title_fullStr Flavokawain A induces apoptosis in MCF-7 and MDA-MB231 and inhibits the metastatic process in vitro
title_full_unstemmed Flavokawain A induces apoptosis in MCF-7 and MDA-MB231 and inhibits the metastatic process in vitro
title_sort flavokawain a induces apoptosis in mcf-7 and mda-mb231 and inhibits the metastatic process in vitro
publisher Public Library of Science
publishDate 2014
url http://psasir.upm.edu.my/id/eprint/37683/1/37683.pdf
http://psasir.upm.edu.my/id/eprint/37683/
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