ROS-Dependent Antiproliferative Effect of Brassinin Derivative Homobrassinin in Human Colorectal Cancer Caco2 Cells

Abstract

This study was designed to examine the in vitro antiproliferative effect of brassinin and its derivatives on human cancer cell lines. Among seven tested compounds, homobrassinin (K1; N-[2-(indol-3-yl)ethyl]-S-methyldithiocarbamate) exhibited the most potent activity with IC 50 = 8.0 μM in human colorectal Caco2 cells and was selected for further studies. The flow cytometric analysis revealed a K1-induced increase in the G 2 /M phase associated with dysregulation of α-tubulin, α 1 -tubulin and β 5 -tubulin expression. These findings suggest that the inhibitory effect of K1 can be mediated via inhibition of microtubule formation. Furthermore, simultaneously with G 2 /M arrest, K1 also increased population of cells with sub-G 1 DNA content which is considered to be a marker of apoptotic cell death. Apoptosis was also confirmed by annexin V/PI double staining, DNA fragmentation assay and chromatin condensation assay. The apoptosis was associated with the loss of mitochondrial membrane potential (MMP), caspase-3 activation as well as OPEN ACCESSMolecules 2014, 19 10878 intracellular reactive oxygen species (ROS) production. Moreover, the antioxidant Trolox blocked ROS production, changes in MMP and decreased K1 cytotoxicity, which confirmed the important role of ROS in cell apoptosis. Taken together, our data demonstrate that K1 induces ROS-dependent apoptosis in Caco2 cells and provide the rationale for further in vivo anticancer investigation.

Leonurine hydrochloride induces apoptosis of H292 lung cancer cell by a mitochondria-dependent pathway

“…Weak changes in MMP can result in a large fall in ATP production and a large increase in ROS production. Plenty of evidence demonstrates that ROS production and consequent oxidative stress cause great damage to mitochondria and tend to induce cell apoptosis (Kello et al, 2014;Pietrowska et al, 2014). Our data demonstrated that LH significant increased the intracellular ROS of H292 cells in a dose-dependent manner ( Figure 4B-1 and B-2).…”

Spirocyclization reactions and antiproliferative activity of indole phytoalexins 1-methoxybrassinin and its 1-substituted derivatives

“…20 Spiroindoline phytoalexins and their derivatives exhibit an antiproliferative effect against human cancer cell lines. 15,[21][22][23][24][25][26] Brassinin (5b) and its synthetic derivative 5-bromobrassinin (5c) act as bioavailable competitive inhibitors of indoleamine 2,3-dioxygenase (IDO), a tryptophan-catabolizing enzyme that promotes tumor escape via a mechanism of immune tolerance. 27,28 1-Methoxybrassinin (5a) displayed significant antiproliferative effect on intramolecular amastigotes of Trypanosoma cruzi and demonstrated a higher potency than shown by the currently used antichagasic agents (nifurtimox, benznidazol).…”

Transferrin-functionalized nanographene oxide for delivery of platinum complexes to enhance cancer-cell selectivity and apoptosis-inducing efficacy

“…Based on this design, we found that Tf-NGO@Pt shows higher anticancer efficacy against MCF human breast cancer cells than the free-Pt complex, and can effectively inhibit cancer-cell migration and invasion by induction of cell apoptosis through upregulation of reactive oxygen species (ROS), important biochemical signaling mediators. [21][22][23][24] In addition, nanolization also enhances the penetration ability and inhibitory effect of the Pt complex toward MCF7 breast cancer-tumor spheroids. The enhancement of anticancer efficacy is positively correlated with the increased amount of cellular uptake and cellular drug retention.…”