Abstract
IntroductionThe 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.MethodsMCF-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.ResultsWe 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.ConclusionsFKA 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.
Highlights
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
We have investigated the effects of flavokawain A (FKA) on the apoptotic and metastatic process in two breast cancer cell lines
Since breast cancer has become the most diagnosed type of cancer in women, especially in Malaysia and generally, worldwide, we aim to investigate the in vitro cytotoxic and anti-metastatic effects of flavokawain A on two types of breast cancer cell lines, MCF-7 and MDA-MB231.Both MCF-7 and MDA-MB231 are well-established breast cancer cell lines but they differ in several aspects including, the p53 status, estrogen receptor status and invasiveness [13]
Summary
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. Kava-kava plant is an evergreen shrub that is widely consumed in the pacific region [7,8] This plant is largely known to be involved in a wide spectrum of biological activities including, antiinflammation, anti-bacterial and most importantly, anti-cancer [9,10]. Since breast cancer has become the most diagnosed type of cancer in women, especially in Malaysia and generally, worldwide, we aim to investigate the in vitro cytotoxic and anti-metastatic effects of flavokawain A on two types of breast cancer cell lines, MCF-7 and MDA-MB231.Both MCF-7 and MDA-MB231 are well-established breast cancer cell lines but they differ in several aspects including, the p53 status, estrogen receptor status and invasiveness [13]. We could assess the effectiveness of flavokawain A in a more wholly approach
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