BYL719, a selective inhibitor of phosphoinositide 3-Kinase α, enhances the effect of selumetinib (AZD6244, ARRY-142886) in KRAS-mutant non-small cell lung cancer.

Purpose: KRAS is frequently mutated in non-small cell lung cancers (NSCLC), resulting in activation of the MEK/ERK pathway. Because there are currently no drugs that target oncogenic KRAS, MEK inhibitors have been tested clinically as a possible treatment option for patients with NSCLC. However, KRAS-mutant cancers exhibit resistance to MEK inhibitors.

Gymnaster koraiensis and its major components, 3,5-di-O-caffeoylquinic acid and gymnasterkoreayne B, reduce oxidative damage induced by tert-butyl hydroperoxide or acetaminophen in HepG2 cells.

We investigated the protective effects of Gymnaster koraiensis against oxidative stress-induced hepatic cell damage. We used two different cytotoxicity models, i.e.

A novel topoisomerase inhibitor, daurinol, suppresses growth of HCT116 cells with low hematological toxicity compared to etoposide.

We report that daurinol, a novel arylnaphthalene lignan, is a promising potential anticancer agent with adverse effects that are less severe than those of etoposide, a clinical anticancer agent. Despite its potent antitumor activity, clinical use of etoposide is limited because of its adverse effects, including myelosuppression and the development of secondary leukemia. Here, we comprehensively compared the mechanistic differences between daurinol and etoposide because they have similar chemical structures.

Isolation of phlorotannins from Eisenia bicyclis and their hepatoprotective effect against oxidative stress induced by tert-butyl hyperoxide.

Eisenia bicyclis (Kjellman) Setchell is a common brown alga that inhabits the middle Pacific coast around Korea and Japan. In this study, the ethanol extract and its serial solvent fractions were prepared from fresh E. bicyclis, and their hepatoprotective effects were investigated against hepatotoxicity in tert-butyl hyperoxide(t-BHP)-injured HepG2 cells.

Cell and nuclear enlargement of SW480 cells induced by a plant lignan, arctigenin: evaluation of cellular DNA content using fluorescence microscopy and flow cytometry.

Arctigenin is a natural plant lignan previously shown to induce G(2)/M arrest in SW480 human colon cancer cells as well as AGS human gastric cancer cells, suggesting its use as a possible cancer chemopreventive agent. Changes in cell and nuclear size often correlate with the functionality of cancer-treating agents. Here, we report that arctigenin induces cell and nuclear enlargement of SW480 cells.

Hepatoprotective effect of flavonoid glycosides from Lespedeza cuneata against oxidative stress induced by tert-butyl hyperoxide.

The aerial parts of Lespedeza cuneata G. Don, perennial legume native to Eastern Asia, have been used therapeutically in traditional Asian medicine to protect the function of liver, kidneys and lungs. However, little is known about the pharmaceutical effect of extracts from this plant.

A polyacetylene from Gymnaster koraiensis exerts hepatoprotective effects in vivo and in vitro.

In the present study, we isolated a polyacetylene, gymnasterkoreayne B (GKB), from Gymnaster koraiensis and investigated the effect of GKB on the protection from oxidative stress-induced cytotoxicity through induction of the expression of cellular defense enzymes. GKB induced mRNA expression and enzyme activity of NAD(P)H:quinone oxidoreductase (NQO1) in vitro and in vivo, and potently increased expression of many cellular defense genes including glutathione-S-transferases, UDP-glucuronosyltransferase, and glutathione reductase (GSR) in normal rat liver. The nuclear factor erythroid 2-related factor 2 (Nrf2) which is known to induce various antioxidant and cytoprotective genes, and the genes containing the antioxidant response element (ARE), including NQO1, hemeoxygenease-1, GSR were induced by GKB in HepG2 human hepatocarcinoma cells.

Lignans inhibit cell growth via regulation of Wnt/beta-catenin signaling.

As aberrant activation of Wnt/beta-catenin signaling is one of the major mechanisms of carcinogenesis in colon cancer, identification of inhibitors of this pathway may aid in colon cancer prevention. We investigated the ability of the lignans arctiin, matairesinol and arctigenin from Saussurea salicifolia to inhibit Wnt/beta-catenin signaling in SW480 human colon cancer cells. The lignans inhibited SW480 cell growth.