Flavokawain A induces apoptosis in MCF-7 and MDA-MB231 and inhibits the metastatic process in vitro.
<h4>Introduction</h4>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 Flavokawa...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2014-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0105244 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849337642881122304 |
|---|---|
| author | Nadiah Abu M Nadeem Akhtar Swee Keong Yeap Kian Lam Lim Wan Yong Ho Aimi Jamil Zulfadli Abdul Rahman Omar Mohd Roslan Sulaiman Mohd Puad Abdullah Noorjahan Banu Alitheen |
| author_facet | Nadiah Abu M Nadeem Akhtar Swee Keong Yeap Kian Lam Lim Wan Yong Ho Aimi Jamil Zulfadli Abdul Rahman Omar Mohd Roslan Sulaiman Mohd Puad Abdullah Noorjahan Banu Alitheen |
| author_sort | Nadiah Abu |
| collection | DOAJ |
| description | <h4>Introduction</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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 |
| id | doaj-art-d51a2b5cdfd14d04a1b3630fdeb4fe4c |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-d51a2b5cdfd14d04a1b3630fdeb4fe4c2025-08-20T03:44:38ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-01910e10524410.1371/journal.pone.0105244Flavokawain A induces apoptosis in MCF-7 and MDA-MB231 and inhibits the metastatic process in vitro.Nadiah AbuM Nadeem AkhtarSwee Keong YeapKian Lam LimWan Yong HoAimi Jamil ZulfadliAbdul Rahman OmarMohd Roslan SulaimanMohd Puad AbdullahNoorjahan Banu Alitheen<h4>Introduction</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.https://doi.org/10.1371/journal.pone.0105244 |
| spellingShingle | Nadiah Abu M Nadeem Akhtar Swee Keong Yeap Kian Lam Lim Wan Yong Ho Aimi Jamil Zulfadli Abdul Rahman Omar Mohd Roslan Sulaiman Mohd Puad Abdullah Noorjahan Banu Alitheen Flavokawain A induces apoptosis in MCF-7 and MDA-MB231 and inhibits the metastatic process in vitro. PLoS ONE |
| title | 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_short | 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 |
| url | https://doi.org/10.1371/journal.pone.0105244 |
| work_keys_str_mv | AT nadiahabu flavokawainainducesapoptosisinmcf7andmdamb231andinhibitsthemetastaticprocessinvitro AT mnadeemakhtar flavokawainainducesapoptosisinmcf7andmdamb231andinhibitsthemetastaticprocessinvitro AT sweekeongyeap flavokawainainducesapoptosisinmcf7andmdamb231andinhibitsthemetastaticprocessinvitro AT kianlamlim flavokawainainducesapoptosisinmcf7andmdamb231andinhibitsthemetastaticprocessinvitro AT wanyongho flavokawainainducesapoptosisinmcf7andmdamb231andinhibitsthemetastaticprocessinvitro AT aimijamilzulfadli flavokawainainducesapoptosisinmcf7andmdamb231andinhibitsthemetastaticprocessinvitro AT abdulrahmanomar flavokawainainducesapoptosisinmcf7andmdamb231andinhibitsthemetastaticprocessinvitro AT mohdroslansulaiman flavokawainainducesapoptosisinmcf7andmdamb231andinhibitsthemetastaticprocessinvitro AT mohdpuadabdullah flavokawainainducesapoptosisinmcf7andmdamb231andinhibitsthemetastaticprocessinvitro AT noorjahanbanualitheen flavokawainainducesapoptosisinmcf7andmdamb231andinhibitsthemetastaticprocessinvitro |