Targeting Histone Methyltransferase DOT1L by a Novel Psammaplin A Analog Inhibits Growth and Metastasis of Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is the most intractable cancer in women with a high risk of metastasis. While hyper-methylation of histone H3 catalyzed by disruptor of telomeric silencing 1-like (DOT1L), a specific methyltransferase for histone H3 at lysine residue 79 (H3K79), is reported as a potential target for TNBCs, early developed nucleoside-type DOT1L inhibitors are not sufficient for effective inhibition of growth and metastasis of TNBC cells. We found that TNBC cells had a high expression level of DOT1L and a low expression level of E-cadherin compared to normal breast epithelial cells and non-TNBC cells.

Effects of SHINBARO2 on Rat Models of Lumbar Spinal Stenosis.

Lumbar spinal stenosis (LSS) is a major cause of chronic low back pain; however, only a few therapies which have been used in clinics still have limited effects on functional recovery. SHINBARO2 is a refined traditional formulation for inflamed lesions and relieve pain of muscular skeletal disease. This study aimed at investigating the effects of SHINBARO2 on LSS and at determining its underlying molecular mechanism in rat models.

Linarin inhibits radiation-induced cancer invasion by downregulating MMP-9 expression via the suppression of NF-κB activation in human non-small-cell lung cancer A549.

Radiotherapy is routinely used in the treatment of lung cancer patients. However, it often causes malignant effects, such as promoting cancer cell migration and invasion. Previous studies demonstrated that ionizing radiation (IR) promotes cancer cell invasion by stimulating the β-catenin, IL-6, STAT3, and Bcl-X signaling pathway or the PI3K, Akt, and NF-κB signaling pathway.

The Anti-Inflammatory Effects of Shinbaro3 Is Mediated by Downregulation of the TLR4 Signalling Pathway in LPS-Stimulated RAW 264.7 Macrophages.

Shinbaro3, a formulation derived from the hydrolysed roots of var. (Engl.) Stapf, has been clinically used in the pharamacopuncture treatment of arthritis in Korea.

Esculetin suppresses tumor growth and metastasis by targeting Axin2/E-cadherin axis in colorectal cancer.

Colorectal cancer (CRC) is the most common malignant disease worldwide due to its metastasis via the epithelial-mesenchymal transition (EMT) process. E-cadherin and Wnt signaling are emerging as potential targets for suppressing the EMT. In this context, Axin2 has been recognized as a negative regulator that inhibits glycogen synthase kinase 3β (GSK3β)-mediated degradation of Snail1, a transcriptional repressor of E-cadherin.

Influence of Boiling Duration of GCSB-5 on Index Compound Content and Antioxidative and Anti-inflammatory Activity.

Background: GCSB-5, an herbal drug composition with an anti-inflammatory effect, is prepared by boiling, which is the most common herbal extraction method in traditional Korean medicine. Several parameters are involved in the process, i.e.

Anti-inflammatory effect of Cortex Eucommiae via modulation of the toll-like receptor 4 pathway in lipopolysaccharide-stimulated RAW 264.7 macrophages.

Ethnopharmocological Relevance: Cortex Eucommiae (CE), the bark of Eucommia ulmoides Oliv., has been traditionally used for its kidney-tonifying and bone- and tendon-enhancing properties in Korea, China, and Japan. CE has been historically prescribed for inflammatory conditions such as arthritis of the knee and ankle.

Anti-Osteoporotic Activity of Harpagoside by Upregulation of the BMP2 and Wnt Signaling Pathways in Osteoblasts and Suppression of Differentiation in Osteoclasts.

Harpagoside (1) is an iridoid glycoside isolated from the radix of Harpagophytum procumbens var. sublobatum, commonly called Devil's claw. The anti-osteoporotic effect of 1 was investigated in both in vitro cell cultures and in vivo using an ovariectomized (OVX) mouse model.

In Vitro and In Vivo Anti-Allergic and Anti-Inflammatory Effects of eBV, a Newly Developed Derivative of Bee Venom, through Modulation of IRF3 Signaling Pathway in a Carrageenan-Induced Edema Model.

Background: Bee venom (BV), a type of toxin extracted from honeybees (Apis mellifera), has been empirically and widely used to treat inflammatory diseases throughout Asia. Essential BV (eBV) was developed by removing phospholipase A2 (PLA2) and histamine to lower occurrence of allergic reaction. This study investigated the anti-allergic and anti-inflammatory activities of eBV in vitro and in vivo and its underlying mechanism of action.

Safety of essential bee venom pharmacopuncture as assessed in a randomized controlled double-blind trial.

Ethnopharmacological Relevance: While bee venom (BV) pharmacopuncture use is common in Asia, frequent occurrence of allergic reactions during the treatment process is burdensome for both practitioner and patient.

Aim Of The Study: This study compared efficacy and safety in isolated and purified essential BV (eBV) pharmacopuncture filtered for phospholipase A2 (PLA2) and histamine sections, and original BV to the aim of promoting safe BV pharmacopuncture use.

Materials And Methods: In in vitro, we examined the effect of BV and eBV on nitric oxide (NO) production induced by lipopolysaccharide (LPS) in RAW 264.

Effects of intra-articular SHINBARO treatment on monosodium iodoacetate-induced osteoarthritis in rats.

Background: SHINBARO is a refined herbal formulation used to treat inflamed lesions and bone diseases. This study aimed to investigate the anti-osteoarthritic activities of intra-articular administration of SHINBARO and determine its underlying molecular mechanism in a monosodium iodoacetate (MIA)-induced osteoarthritis rat model.

Methods: Male Sprague-Dawley rats received a single intra-articular injection of MIA into the infrapatellar ligament of the right knee.

Antitumor Activity of Spicatoside A by Modulation of Autophagy and Apoptosis in Human Colorectal Cancer Cells.

The antitumor activity of spicatoside A (1), a steroidal saponin isolated from the tuber of Liriope platyphylla, and its underlying mechanisms were investigated in HCT116 human colorectal cancer cells. Compound 1 induced autophagy and apoptotic cell death and inhibited tumor growth in a nude mouse xenograft model implanted with HCT116 cells. Treatment with 1 for 24 h enhanced the formation of acidic vesicular organelles in the cytoplasm, indicating the induction of the onset of autophagy.

Anti-osteoporotic activity of harpagide by regulation of bone formation in osteoblast cell culture and ovariectomy-induced bone loss mouse models.

Ethnopharmacological Relevance: Harpagide, an iridoid glucoside, is a constituent of the root of Harpagophytum procumbens var. sublobatum (Engl.) Stapf, Devil's claw which has been used in patients with osteoarthritis (OA).

Anti-tumoral effect of arsenic compound, sodium metaarsenite (KML001), in non-Hodgkin's lymphoma: an in vitro and in vivo study.

Arsenic compounds have been used in traditional medicine for several centuries. KML001 (sodium metaarsenite; NaAsO2) is an orally bio-available arsenic compound with potential anti-cancer activity. However, the effect of KML001 has not been studied in lymphoid neoplasms.

Induction of Cell Cycle Arrest and Apoptosis by Physcion, an Anthraquinone Isolated From Rhubarb (Rhizomes of Rheum tanguticum), in MDA-MB-231 Human Breast Cancer Cells.

Background: Physcion is an anthraquinone from rhubarb (rhizomes of Rheum tanguticum) and has been reported to have anti-inflammatory, hepatoprotective, antifungal, and anti-cancer activities. However, the growth inhibitory activity against human cancer cells and the underlying molecular mechanisms have been poorly determined. This study was designed to investigate the anti-proliferative activity of physcion by induction of cell cycle arrest and apoptosis in human MDA-MB-231 triple negative breast cancer cell line.

Effects of JSOG-6 on protection against bone loss in ovariectomized mice through regulation of osteoblast differentiation and osteoclast formation.

Background: JSOG-6 is used as a traditional medicine to relieve the symptoms associated with inflammation, rheumatism, and osteoporosis in Korea. In the present study, we investigated the effects of JSOG-6 on bone loss prevention both in in vitro and in vivo as well as its underlying mechanism of action.

Methods: Protection against bone loss was assessed in an ovariectomized (OVX) mouse model.

Suppression of inducible nitric oxide synthase expression by nyasol and broussonin A, two phenolic compounds from Anemarrhena asphodeloides, through NF-κB transcriptional regulation in vitro and in vivo.

Anemarrhena asphodeloides is widely used in traditional Chinese medicine, and is known to possess antidiabetic and anti-inflammatory properties. Because inducible nitric oxide synthase (iNOS) plays an important role in inflammation, we investigated the inhibitory effects of two known phenolic compounds, nyasol (1) and broussonin A (2), from A. asphodeloides, on iNOS and its plausible mechanism of action.

Suppression of inflammatory responses by handelin, a guaianolide dimer from Chrysanthemum boreale, via downregulation of NF-κB signaling and pro-inflammatory cytokine production.

The anti-inflammatory activity of handelin (1), a guaianolide dimer from Chrysanthemum boreale flowers, was evaluated in vivo, and the effects on mediators nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) and the nuclear factor-κB (NF-κB) and ERK/JNK signaling pathways were investigated in vitro. Compound 1 inhibited lipopolysaccharide (LPS)-induced production of NO and PGE2 in cultured mouse macrophage RAW 264.7 cells.

Antitumor activity of 2-hydroxycinnamaldehyde for human colon cancer cells through suppression of β-catenin signaling.

The antiproliferative and antitumor activities of 2-hydroxycinnamaldehyde (1), a phenylpropanoid isolated from the bark of Cinnamomum cassia, were investigated using human colorectal cancer cells. Compound 1 exhibited antiproliferative effects in HCT116 colon cancer cells, accompanied by modulation of the Wnt/β-catenin cell signaling pathway. This substance was found also to inhibit β-catenin/T-cell factor (TCF) transcriptional activity in HEK293 cells and HCT116 colon cancer cells.

Suppression of Src/ERK and GSK-3/β-catenin signaling by pinosylvin inhibits the growth of human colorectal cancer cells.

Pinosylvin, a naturally occurring trans-stilbenoid mainly found in Pinus species, has exhibited a potential cancer chemopreventive activity. However, the growth inhibitory activity against cancer cells and the underlying molecular mechanisms remain to be elucidated. Therefore, the anti-proliferative activity of pinosylvin was investigated in human colorectal HCT 116 cancer cells.

Design, synthesis, and evaluation of a water-soluble antofine analogue with high antiproliferative and antitumor activity.

New water soluble antofine C-13a analogues were designed, synthesized, and evaluated for antiproliferative activity against cancer cells. Particularly, (-)-(R)-13a-hydroxymethylantofine ((-)-(R)-4b) demonstrated notable growth inhibition against a panel of human cancer cell lines. This growth inhibition was associated with the arrest of the cell cycle in the G0/G1 phases and suppression of mTOR signaling in human lung A549 cancer cells.

In vitro stability and in vivo anti-inflammatory efficacy of synthetic jasmonates.

A chlorinated methyl jasmonate analog (J7) was elaborated as an in vitro anti-inflammatory lead. However, its in vitro efficacy profile was not reproduced in a subsequent in vivo evaluation, presumably due to its rapid enzymatic hydrolysis in a biological system. In an attempt to improve the metabolic stability of the lead J7 by replacement of its labile methyl ester with reasonable ester groups, several analogs resistant to enzymatic hydrolysis were synthesized.

Wnt/β-catenin signaling mediates the antitumor activity of magnolol in colorectal cancer cells.

Abnormal activation of the canonical Wnt/β-catenin pathway and up-regulation of the β-catenin/T-cell factor (TCF) response to transcriptional signaling play a critical role early in colorectal carcinogenesis. Therefore, Wnt/β-catenin signaling is considered an attractive target for cancer chemotherapeutic or chemopreventive agents. Small molecules derived from the natural products were used in our cell-based reporter gene assay to identify potential inhibitors of Wnt/β-catenin signaling.