Flavokawain B induced cytotoxicity in two breast cancer cell lines, MCF-7 and MDA-MB231 and inhibited the metastatic potential of MDA-MB231 via the regulation of several tyrosine kinases In vitro

Abstract

BackgroundThe kava-kava plant (Piper methysticum) is traditionally consumed by the pacific islanders and has been linked to be involved in several biological activities. Flavokawain B is a unique chalcone, which can be found in the roots of the kava-kava plant. In this study, the operational mechanism of the anti-cancer activity of a synthetic Flavokawain B (FKB) on two breast cancer cell lines, MCF-7 and MDA-MB231 was investigated.MethodSeveral in vitro assays were attempted such as MTT, flow cytometry of cell cycle analysis, annexin V analysis, and JC-1 analysis to detect apoptosis. Moreover, in vitro metastasis assays were also performed such as transwell migration assay, invasion assay, rat aorta ring and HUVEC tube formation. Molecular analysis of related genes and proteins were conducted using real-time PCR and proteome profiler analysis.ResultsBased on our results, apoptosis was induced when both MCF-7 and MDA-MB231 were treated with FKB. A significant G2/M arrest was seen in MDA-MB231 cells. Additionally, FKB also inhibited the in vitro migration and invasion in MDA-MB231 cells in a dose dependent manner. Moreover, FKB can be a potential inhibitor in angiogenesis as it suppressed the formation of vessels in HUVEC cells as well as in the ex-vivo rat aortic ring assay.ConclusionOur findings suggested that FKB also regulated several receptor tyrosine kinases. Overall, FKB is not only a potential candidate to be an anti-cancer agent, but as an anti-metastatic agent as well.Electronic supplementary materialThe online version of this article (doi:10.1186/s12906-016-1046-8) contains supplementary material, which is available to authorized users.

Crude Extracts, Flavokawain B and Alpinetin Compounds from the Rhizome of Alpinia mutica Induce Cell Death via UCK2 Enzyme Inhibition and in Turn Reduce 18S rRNA Biosynthesis in HT-29 Cells

“…These IC 50 values are, however 6 fold lower than that observed in colorectal cancer (HT-29 and HCT 116 cells), which in fact, is within acceptable concentration limits. In one related study, inhibition of two breast cancer cells by FKB at an IC 50 of 12.3 and 33.8 μM in MDA-MB231 and MCF-7, respectively were reported [19]. APN on the other hand, have been previously reported to inhibit HCT 116 cells at an IC 50 of 39.6 μg/mL [20].…”

“…Previous study conducted had shown that FKB induced cell cycle arrest at G2/M phase in HCT116 [16], SK-LMS-1 and ECC-1 [17], 143B and SaOS-2 [18], and MDA-MB231 and MCF-7 [19]. On the contrary, findings in this current investigation seem to suggest that increasing dead cells accumulated at subG0/G1 phase instead, rather than blocking cell progression at G2/M phase.…”

The protective effects of Kava (Piper Methysticum) constituents in cancers: A systematic review

“…A total of 21 studies, comprising 15 in vitro (including 2 in situ; 1 ex vivo), 1 in vivo, and 5 that assessed both models, examined the anticancer effects of FKB. Across these studies, there was unanimous agreement that FKB had antiproliferative ability with the majority of papers reporting induction of G2/M arrest . One paper suggested FKB induced G0/G1 arrest .…”

“…One paper suggested FKB induced G0/G1 arrest . Additionally, there was a general consensus that FKB induced apoptosis . Proposed mechanisms included increased expression of pro‐apoptotic proteins, such as PUMA, Bim and Bax expression; decreased expression of anti‐apoptotic proteins, such as survivin and XIAP, ROS production; or increase in caspase 3, 7, 8, and or 9 .…”

“…A number of studies investigated angiogenesis‐inhibitory properties and found Kava compounds successfully inhibited vessel formation in vivo and in vitro . Both FKA and FKB were shown to reduce angiogenesis in a dose‐dependent manner . For instance, FKA was found to downregulate the androgen receptor and subsequently alter angiogenesis in bladder tumour tissues …”