Butein suppresses breast cancer growth by reducing a production of intracellular reactive oxygen species

Abstract

BackgroundButein has various functions in human diseases including cancer. While anti-cancer effects of butein have been revealed, it is urgent to understand a unique role of butein against cancer. In this study, we demonstrate that butein inhibition of reactive oxygen species (ROS) production results in suppression of breast cancer growth.MethodsDifferent breast cancer cell lines were treated with butein and then subjected to cell viability and apoptosis assays. Butein-sensitive or -resistant breast cancer cells were injected into mammary fat pads of immunocompromised mice and then butein was injected. Breast cancer cells were categorized on the basis of butein sensitivity.ResultsButein reduced viabilities of different breast cancer cells, while not affecting those of HER2-positive (HER2+) HCC-1419, SKBR-3 and HCC-2218 breast cancer cells. Butein reduction of ROS levels was correlated with apoptotic cell death. Furthermore, butein reduction of ROS level led to inhibitions of AKT phosphorylation. N-acetyl-L-cysteine (NAC), a free radical scavenger, also reduced ROS production and AKT phosphorylation, resulting in apoptotic cell death. In contrast, inhibitory effects of both butein and NAC on ROS production and AKT phosphorylation were not detected in butein-resistant HER2+ HCC-1419, SKBR-3 and HCC-2218 cells. In the in vivo tumor growth assays, butein inhibited tumor growth of butein-sensitive HER2+ BT-474 cells, while not affecting that of butein-resistant HER2+ HCC-1419 cells. Moreover, butein inhibition of ROS production and AKT phosphorylation was confirmed by in vivo tumor growth assays.ConclusionsOur study first reveals that butein causes breast cancer cell death by the reduction of ROS production. Therefore, our finding provides better knowledge for butein effect on breast cancer and also suggests its treatment option.

Naringenin inhibits migration of lung cancer cells via the inhibition of matrix metalloproteinases-2 and −9

“…Cells were treated with different concentrations of naringenin for 24 h and seeded at a density of 5x10 5 /ml in the upper chamber of the 48-well Boyden chamber (Merck Millipore). The lower chamber contained 20% FBS.…”

“…For example, butein inhibits the migration and invasion of bladder cancer cells by reducing the expression of extracellular signal-regulated kinase 1/2 and its activities (3). In addition, butein has been found to elevate reactive oxygen species (ROS) levels and trigger apoptosis in neuroblastoma (4) and breast cancer cells (5,6). Moreover, shikonin induces apoptosis in osteosarcoma cells via the generation of ROS (7).…”

Antioxidant and antimalarial properties of butein and homobutein based on their ability to chelate iron (II and III) cations: a DFT study in vacuo and in solution

“…These compounds have been reported to possess numerous biological activities such as vasorelaxant [6], antitumor [7][8][9][10][11], antiinflammation [10,11], antimalarial [12][13][14], antiplasmodial [13,14] and antioxidant [15][16][17][18][19][20][21]. For instance, butein has shown antioxidant activity against lipid and low-density lipoprotein peroxidation by its free radical scavenging action and metal ion chelation ability [15,16,[18][19][20][21].…”

The inhibitory effects of butein on cell proliferation and TNF-α-induced CCL2 release in racially different triple negative breast cancer cells

“…Polyphenolic compounds have received considerable attention for their use as a cancer chemopreventive and a chemotherapeutic agent. Previous in vitro studies showed butein cytotoxic and anti-proliferative effects on breast cancer cells, including MDA-MB-231 and MCF-7 [13,53], suggesting that butein might have similar effects in other breast cancer cell lines. However, there is no data comparing the effect of this compound in racially different TNBC cells.…”