Inhibitory effect of trans-ferulic acid on proliferation and migration of human lung cancer cells accompanied with increased endogenous reactive oxygen species and β-catenin instability

Abstract

BackgroundTrans-ferulic (FA) acid exhibits antioxidant effects in vitro. However, the underlying mechanism of trans-FA activity in cellular physiology, especially cancer physiology, remains largely unknown. This study investigated the cellular physiological effects of trans-FA on the H1299 human lung cancer cell line.MethodsThe 2,2-diphenyl-1-picrylhydrazyl assay was used to determine free radical scavenging capability. Assessment of intracellular reactive oxygen species (ROS) was evaluated using oxidized 2ʹ,7ʹ-dichlorofluorescin diacetate and dihydroethidium staining. Trypan blue exclusion, colony formation, and anchorage-independent growth assays were used to determine cellular proliferation. Annexin V staining assay was used to assess cellular apoptosis by flow cytometry. Wound healing and Boyden’s well assays were used to detect the migration and invasion of cells. Gelatin zymography was used to detect matrix metalloproteinase (MMP-2 and MMP-9) activity. Western blotting was used to detect expression levels of various signaling pathway proteins.ResultsDPPH assay results indicated that trans-FA exerted potent antioxidant effects. However, trans-FA increased intracellular ROS levels, including hydrogen peroxide and superoxide anion, in H1299 cells. Trans-FA treatment inhibited cellular proliferation and induced moderate apoptotic cell death at the highest concentration used (0.6 mM). Furthermore, trans-FA moderately inhibited the migration of H1299 cells at the concentrations of 0.3 and 0.6 mM and attenuated MMP-2 and MMP-9 activity. Trans-FA caused the phosphorylation of β-catenin, resulting in proteasomal degradation of β-catenin. Conversely, trans-FA treatment increased the expression of pro-apoptotic factor Bax and decreased the expression of pro-survival factor survivin.ConclusionVarious concentrations (0.06–0.6 mM) of trans-FA exert both anti-proliferation and anti-migration effects in the human lung cancer cell line H1299.Electronic supplementary materialThe online version of this article (doi:10.1186/s13020-016-0116-7) contains supplementary material, which is available to authorized users.

Ethanol extract of Ophiorrhiza pumila suppresses liver cancer cell proliferation and migration

“…Increased ROS production is considered to be an important factor controlling cell survival and apoptosis [18][19][20]. The effect of OPE on ROS generation was examined using DCFH-DA staining.…”

Characterization and anti-tumor activity of a polysaccharide isolated from Dendrobium officinale grown in the Huoshan County

“…In addition to ROS and mitochondrial function, we also evaluated the effects of DOPA-1 treatment on apoptosis-related protein expression. As a major modulator of apoptosis, the Bcl-2 protein family controls the release of mitochondrial apoptosis-inducing factors [ 31 ], which can be divided into pro-apoptotic proteins (such as Bax, Bak, and Bid) and anti-apoptotic proteins (such as Bcl-2, Bcl-xL, and Bcl-w) [ 32 ]. In this study, we found that DOPA-1 decreases Bcl-2 expression, while increasing Bax expression in HepG-2 cells.…”

<em>Glinus oppositifolius</em> (L.) Aug. DC.: A Repository of Medicinal Potentiality

“…The sources of the chemical compounds were either synthetic, or from a plant other than Glinus oppositifolius. Several chemical compounds like benzoic acid [47], trans-ferulic acid [48][49][50][51], vanillin [52], stigmasterol [53], spinasterol [54,55], β-sitosterol [56][57][58][59][60][61][62][63][64][65][66][67][68], vitexin [69], vicenin [70], kaempferol [71] showed anti-cancer effects against breast cancer cell lines, prostate cancer cell lines, colon cancer cell lines, stomach cancer cell lines, leukaemia (Table 1). β-sitosterol acts through down-regulation of Bcl-2 and upregulation of Bax, thereby causing caspase 3 cleavage and PARP cleavage and thereby causes apoptosis (Figure. (Table 2).…”