Taiwan cobra cardiotoxin III suppresses EGF/EGFR-mediated epithelial-to-mesenchymal transition and invasion of human breast cancer MDA-MB-231 cells.

Breast cancer is a highly malignant carcinoma and most deaths of breast cancer are caused by metastasis. The epithelial-to-mesenchymal transition (EMT) has emerged as a pivotal event in the development of the invasive and metastatic potentials of cancer progression. Epidermal growth factor (EGF) and its receptor, EGFR, play roles in cancer metastasis.

BPIQ, a novel synthetic quinoline derivative, inhibits growth and induces mitochondrial apoptosis of lung cancer cells in vitro and in zebrafish xenograft model.

Background: 2,9-Bis[2-(pyrrolidin-1-yl)ethoxy]-6-{4-[2-(pyrrolidin-1-yl)ethoxy] phenyl}-11H-indeno[1,2-c]quinolin-11-one (BPIQ) is a derivative from 6-arylindeno[1,2-c]quinoline. Our previous study showed the anti-cancer potential of BPIQ compared to its two analogues topotecan and irinotecan. In the study, the aim is to investigate the potency and the mechanism of BPIQ against lung cancer cells.

Cardiotoxin III Inhibits Hepatocyte Growth Factor-Induced Epithelial-Mesenchymal Transition and Suppresses Invasion of MDA-MB-231 Cells.

The epithelial-mesenchymal transition (EMT) is the first step required for breast cancer to initiate metastasis. In this study, hepatocyte growth factor (HGF) was used as a metastatic inducer of MDA-MB-231 cells. Cardiotoxin III (CTX III) inhibited HGF-induced morphological changes and upregulation of E-cadherin with the concomitant decrease in N-cadherin and Vimentin protein levels, resulting in inhibition of cell migration and invasion.

Quinacrine induces apoptosis in human leukemia K562 cells via p38 MAPK-elicited BCL2 down-regulation and suppression of ERK/c-Jun-mediated BCL2L1 expression.

Although previous studies have revealed the anti-cancer activity of quinacrine, its effect on leukemia is not clearly resolved. We sought to explore the cytotoxic effect and mechanism of quinacrine action in human leukemia K562 cells. Quinacrine induced K562 cell apoptosis accompanied with ROS generation, mitochondrial depolarization, and down-regulation of BCL2L1 and BCL2.

Modulated mechanism of phosphatidylserine on the catalytic activity of Naja naja atra phospholipase A2 and Notechis scutatus scutatus notexin.

Phosphatidylserine (PS) externalization is a hallmark for apoptotic death of cells. Previous studies showed that Naja naja atra phospholipase A2 (NnaPLA2) and Notechis scutatus scutatus notexin induced apoptosis of human cancer cells. However, NnaPLA2 and notexin did not markedly disrupt the integrity of cellular membrane as evidenced by membrane permeability of propidium iodide.

Cardiotoxin III suppresses hepatocyte growth factor-stimulated migration and invasion of MDA-MB-231 cells.

The hepatocyte growth factor (HGF)/c-Met signalling pathway is deregulated in most cancers and associated with a poor prognosis in breast cancer. Cardiotoxin III (CTX III), a basic polypeptide isolated from Naja naja atra venom, has been shown to exhibit anticancer activity. In this study, we use HGF as an invasive inducer to investigate the effect of CTX III on MDA-MB-231 cells.

Inhibitory action of naphtho[1,2-b]furan-4,5-dione on hepatocyte growth factor-induced migration and invasion of MDA-MB-231 cells: mechanisms of action.

Naphtho[1,2-b]furan-4,5-dione (NFD), a bioactive component of Avicennia marina, has been shown to exhibit anticancer activity. The aim of the present study was to explore the effect of NFD on hepatocyte growth factor (HGF)-induced cell migration and invasion of MDA-MB-231 human breast cancer cells, as well as the underlying mechanism of action. Cell viability was determined using the 3-(4,5-dimethyl-2 thiazoyl)-2,5-diphenyl-2H-tetrazolium bromide assay, western blot analysis was used to measure protein expression and cell migration and invasion were evaluated by the cell wound healing assay, Boyden chamber assay and gelatin zymography.

Taiwan cobra phospholipase A2 suppresses ERK-mediated ADAM17 maturation, thus reducing secreted TNF-α production in human leukemia U937 cells.

The goal of this study was to explore the signaling pathway regulating the processing of proADAM17 into ADAM17 in Taiwan cobra phospholipase A2 (PLA2)-treated human leukemia U937 cells. PLA2 induced reactive oxygen species (ROS)-elicited p38 MAPK activation and ERK inactivation in U937 cells. Catalytically inactive bromophenacylated PLA2 (BPB-PLA2) and PLA2 mutants evoked Ca(2+)-mediated p38 MAPK activation, and the level of phosphorylated ERK remained unchanged.

Naphtho[1,2-b]furan-4,5-dione inhibits MDA-MB-231 cell migration and invasion by suppressing Src-mediated signaling pathways.

Naphtho[1,2-b]furan-4,5-dione (NFD), a bioactive component of Avicennia marina, has been demonstrated to display anti-cancer activity. Breast cancer is a highly malignant carcinoma and most deaths of breast cancer are caused by metastasis. In this study, we showed that NFD blocked migration and invasion of MDA-MB-231 breast cancer cells without affecting apoptosis or growth arrest.

Inhibition of Src activation with cardiotoxin III blocks migration and invasion of MDA-MB-231 cells.

Cardiotoxin III (CTX III), a basic polypeptide isolated from Naja naja atra venom, has been demonstrated to display anticancer activity. Breast cancer is a highly malignant carcinoma and most deaths of breast cancer are caused by metastasis. In this study, we show that CTX III blocks migration and invasion of MDA-MB-231 breast cancer cells without affecting apoptosis or cell cycle arrest.

Cardiotoxin III inhibits proliferation and migration of oral cancer cells through MAPK and MMP signaling.

Cardiotoxin III (CTXIII), isolated from the snake venom of Formosan cobra Naja naja atra, has previously been found to induce apoptosis in many types of cancer. Early metastasis is typical for the progression of oral cancer. To modulate the cell migration behavior of oral cancer is one of the oral cancer therapies.

Brazilein suppresses migration and invasion of MDA-MB-231 breast cancer cells.

Brazilein, a bioactive compound isolated from Caesalpinia sappan L., has long been used in oriental folk medicines. Cancer metastasis is a primary cause of cancer death.

Cross talk between p38MAPK and ERK is mediated through MAPK-mediated protein phosphatase 2A catalytic subunit α and MAPK phosphatase-1 expression in human leukemia U937 cells.

This study explores the signaling transduction cascade of ERK and p38 MAPK on regulating MAPK phosphatase-1 (MKP-1) and protein phosphatase 2A catalytic subunit α (PP2Acα) expression in caffeine-treated human leukemia U937 cells. Caffeine induced an increase in the intracellular Ca(2+) concentration and ROS generation leading to p38 MAPK activation and ERK inactivation, respectively. Caffeine treatment elicited MKP-1 down-regulation and PP2Acα up-regulation.

Fusogenicity of Naja naja atra cardiotoxin-like basic protein on sphingomyelin vesicles containing oxidized phosphatidylcholine and cholesterol.

This study investigated the effect of oxidized phosphatidylcholine (oxPC) and cholesterol (Chol) on Naja naja atra cardiotoxin-like basic protein (CLBP)-induced fusion and leakage in sphingomyelin (SM) vesicles. Compared with those on PC/SM/Chol vesicles, CLBP showed a lower activity to induce membrane permeability but a higher fusogenicity on oxPC/SM/Chol vesicles. A reduction in inner-leaflet fusion elucidated that CLBP fusogenicity was not in parallel to its membrane-leakage activity on oxPC/SM/Chol vesicles.

Inhibition of EGF/EGFR activation with naphtho[1,2-b]furan-4,5-dione blocks migration and invasion of MDA-MB-231 cells.

Naphtho[1,2-b]furan-4,5-dione (NFD), a bioactive component of Avicennia marina, has been demonstrated to display anti-cancer activity. Activation of epidermal growth factor receptor (EGFR)-induced signaling pathway has been correlated with cancer metastasis in various tumors, including breast carcinoma. We use EGF as a metastatic inducer of MDA-MB-231 cells to investigate the effect of NFD on cell migration and invasion.

Cardiotoxin III suppresses MDA-MB-231 cell metastasis through the inhibition of EGF/EGFR-mediated signaling pathway.

Cardiotoxin III (CTX III), a basic polypeptide isolated from Naja naja atra venom, has been shown to exhibit anticancer activity. Epidermal growth factor (EGF) and its receptor, EGFR, play roles in cancer metastasis in various tumors. We use EGF as a metastatic inducer of MDA-MB-231 cells to investigate the effect of CTX III on cell migration.

Quercetin modulates activities of Taiwan cobra phospholipase A2 via its effects on membrane structure and membrane-bound mode of phospholipase A2.

The goal of the present study is to elucidate the mechanism of quercetin on modulating Naja naja atra phospholipase A2 (PLA2) activities. Sphingomyelin inhibited PLA2 enzymatic activity and membrane-damaging activity against egg yolk phosphatidylcholine (EYPC), while cholesterol and quercetin abrogated the sphingomeyelin inhibitory effect. Quercetin incorporation led to a reduction in PLA2 enzymatic activity and membrane-damaging activity toward EYPC/sphingomyelin/cholesterol vesicles.

Naja naja atra and Naja nigricollis cardiotoxins induce fusion of Escherichia coli and Staphylococcus aureus membrane-mimicking liposomes.

Our previous studies showed that the bactericidal effect of Naja naja atra cardiotoxin 3 (CTX3) and Naja nigricollis toxin γ was associated with their membrane-damaging activity. To elucidate the mechanism responsible for CTX3- and toxin γ-induced membrane permeability, we investigated the interacted mode of CTX3 and toxin γ with model membrane of Escherichia coli (phosphatidylethanolamine (PE)/phosphatidylglycerol (PG), mol/mol, 75/25) and Staphylococcus aureus (PG/cardiolipin, mol/mol, 60/40) in this study. Membrane-damaging activity of toxin γ on PE/PG and PG/cardiolipin vesicles were similar, while CTX3-induced leakage of PG/cardiolipin vesicles was notably higher than that of PE/PG vesicles.

Furano-1,2-Naphthoquinone Inhibits Src and PI3K/Akt Signaling Pathways in Ca9-22 Human Oral Squamous Carcinoma Cells.

Furano-1,2-naphthoquinone (FNQ), a biologically active component ofAvicennia marina, has been demonstrated to display anticancer activity. FNQ exerted cytotoxicity with the G2/M cell cycle arrest and apoptosis in Ca9-22 cells. FNQ-induced G2/M arrest was correlated with a marked decrease in the expression levels of cyclin A and cyclin B, and their activating partner cyclin-dependent kinases (CDK) 1 and 2 with concomitant induction of p27.

Antimetastatic potential of cardiotoxin III involves inactivation of PI3K/Akt and p38 MAPK signaling pathways in human breast cancer MDA-MB-231 cells.

Aim: The aim of this study is to determine whether cardiotoxin III (CTX III) inhibited the metastasis in MDA-MB-231 cells and to further explain its possible mechanisms.

Main Methods: The MTT assay, wound healing assay, Boyden chamber invasion assay, zymography analysis, reverse transcriptase polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), inhibitor assay, and Western blot analysis were used to reveal molecular events of CTX III in this study.

Key Findings: During treatment with non-toxic doses of CTX III, not only cell migration and invasion were markedly suppressed but the expression/activity of matrix metalloproteinase-9 (MMP-9) was also significantly and selectively suppressed in a concentration-dependent manner.

Antimetastatic effect and mechanism of ovatodiolide in MDA-MB-231 human breast cancer cells.

Cancer metastasis is a primary cause of cancer death. Ovatodiolide, a bioactive cembrane-type diterpenoid isolated from Anisomeles indica (L.) Kuntze (Labiatae), has been shown to inhibit the growth and proliferation of cancer cells.

Guanidination of notexin promotes its phospholipase A(2) activity-independent fusogenicity on vesicles with lipid-supplied negative curvature.

To address the requirement of phospholipase A(2) (PLA(2)) activity in membrane fusion events and membrane perturbation activity of notexin and guanidinated notexin (Gu-notexin), the present study was conducted. Notexin and Gu-notexin did not show PLA(2) activity after the removal of Ca(2+) with EDTA. Metal-free notexin and Gu-notexin were found to induce membrane leakage and fusion of phospholipid vesicles.

Phospholipase A2 activity-dependent and -independent fusogenic activity of Naja nigricollis CMS-9 on zwitterionic and anionic phospholipid vesicles.

CMS-9, a phospholipase A(2) (PLA(2)) from Naja nigricollis venom, induced the death of human breast cancer MCF-7 cells accompanied with the formation of cell clumps without clear boundaries between cells. Annexin V-FITC staining indicated that abundant phosphatidylserine appeared on the outer membrane of MCF-7 cell clumps, implying the possibility that CMS-9 may promote membrane fusion via anionic phospholipids. To validate this proposition, fusogenic activity of CMS-9 on vesicles composed of zwitterionic phospholipid alone or a combination of zwitterionic and anionic phospholipids was examined.

Membrane-damaging activity of Taiwan cobra cardiotoxin 3 is responsible for its bactericidal activity.

This study investigates the causal relationship between membrane-damaging activity and bactericidal activity of Naja naja atra (Taiwan cobra) cardiotoxin 3 (CTX3). CTX3 showed greater inhibitory activity for the growth of Staphylococcus aureus (Gram-positive bacteria) relative to that of Escherichia coli (Gram-negative bacteria). The CTX3 antibacterial activity is positively correlated with the increase in membrane permeability of bacterial cells.

Sphingomyelin modulates interfacial binding of Taiwan cobra phospholipase A2.

The goal of the present study is to elucidate the effect of sphingomyelin on interfacial binding of Taiwan cobra phospholipase A(2) (PLA(2)). Substitution of Asn-1 with Met caused a reduction in enzymatic activity and membrane-damaging activity of PLA(2) toward phospholipid vesicles, while sphingomyelin exerted an inhibitory effect on the biological activities of native and mutated PLA(2). Incorporation of sphingomyelin reduced membrane fluidity of phospholipid vesicles as evidenced by Laurdan fluorescence measurement.