Flavokawain A Induces Apoptosis in MCF-7 and MDAMB231 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:	Akhtar, Muhammad Nadeem, Noorjahan Banu, Alitheen, Mohd Puad, Abdullah, Mohd Roslan, Sulaiman, Abdul Rahman, Omar, Aimi Jamil, Zulfadli, Ho, Wan Yong, Lim, Kian Lam, Yeap, Swee Keong, Nadiah, Abu
Format:	Article
Language:	English
Published:	Public Library of Science
Subjects:	QD Chemistry
Online Access:	http://umpir.ump.edu.my/id/eprint/7987/ http://umpir.ump.edu.my/id/eprint/7987/ http://umpir.ump.edu.my/id/eprint/7987/1/Dr.Nadeem_Q1journal.pone.0105244.pdf

id	ump-7987
recordtype	eprints
spelling	ump-79872019-07-09T06:21:06Z http://umpir.ump.edu.my/id/eprint/7987/ Flavokawain A Induces Apoptosis in MCF-7 and MDAMB231 and Inhibits the Metastatic Process In Vitro Akhtar, Muhammad Nadeem Noorjahan Banu, Alitheen Mohd Puad, Abdullah Mohd Roslan, Sulaiman Abdul Rahman, Omar Aimi Jamil, Zulfadli Ho, Wan Yong Lim, Kian Lam Yeap, Swee Keong Nadiah, Abu QD Chemistry 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 Article PeerReviewed pdf en cc_by_4 http://umpir.ump.edu.my/id/eprint/7987/1/Dr.Nadeem_Q1journal.pone.0105244.pdf Akhtar, Muhammad Nadeem and Noorjahan Banu, Alitheen and Mohd Puad, Abdullah and Mohd Roslan, Sulaiman and Abdul Rahman, Omar and Aimi Jamil, Zulfadli and Ho, Wan Yong and Lim, Kian Lam and Yeap, Swee Keong and Nadiah, Abu Flavokawain A Induces Apoptosis in MCF-7 and MDAMB231 and Inhibits the Metastatic Process In Vitro. PLoS ONE. ISSN 1932-6203 http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0105244
repository_type	Digital Repository
institution_category	Local University
institution	Universiti Malaysia Pahang
building	UMP Institutional Repository
collection	Online Access
language	English
topic	QD Chemistry
spellingShingle	QD Chemistry Akhtar, Muhammad Nadeem Noorjahan Banu, Alitheen Mohd Puad, Abdullah Mohd Roslan, Sulaiman Abdul Rahman, Omar Aimi Jamil, Zulfadli Ho, Wan Yong Lim, Kian Lam Yeap, Swee Keong Nadiah, Abu Flavokawain A Induces Apoptosis in MCF-7 and MDAMB231 and Inhibits the Metastatic Process In Vitro
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	Akhtar, Muhammad Nadeem Noorjahan Banu, Alitheen Mohd Puad, Abdullah Mohd Roslan, Sulaiman Abdul Rahman, Omar Aimi Jamil, Zulfadli Ho, Wan Yong Lim, Kian Lam Yeap, Swee Keong Nadiah, Abu
author_facet	Akhtar, Muhammad Nadeem Noorjahan Banu, Alitheen Mohd Puad, Abdullah Mohd Roslan, Sulaiman Abdul Rahman, Omar Aimi Jamil, Zulfadli Ho, Wan Yong Lim, Kian Lam Yeap, Swee Keong Nadiah, Abu
author_sort	Akhtar, Muhammad Nadeem
title	Flavokawain A Induces Apoptosis in MCF-7 and MDAMB231 and Inhibits the Metastatic Process In Vitro
title_short	Flavokawain A Induces Apoptosis in MCF-7 and MDAMB231 and Inhibits the Metastatic Process In Vitro
title_full	Flavokawain A Induces Apoptosis in MCF-7 and MDAMB231 and Inhibits the Metastatic Process In Vitro
title_fullStr	Flavokawain A Induces Apoptosis in MCF-7 and MDAMB231 and Inhibits the Metastatic Process In Vitro
title_full_unstemmed	Flavokawain A Induces Apoptosis in MCF-7 and MDAMB231 and Inhibits the Metastatic Process In Vitro
title_sort	flavokawain a induces apoptosis in mcf-7 and mdamb231 and inhibits the metastatic process in vitro
publisher	Public Library of Science
url	http://umpir.ump.edu.my/id/eprint/7987/ http://umpir.ump.edu.my/id/eprint/7987/ http://umpir.ump.edu.my/id/eprint/7987/1/Dr.Nadeem_Q1journal.pone.0105244.pdf
first_indexed	2023-09-18T22:05:12Z
last_indexed	2023-09-18T22:05:12Z
_version_	1777414661831917568

Flavokawain A Induces Apoptosis in MCF-7 and MDAMB231 and Inhibits the Metastatic Process In Vitro

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