Role of CSF1R 550th-tryptophan in kusunokinin and CSF1R inhibitor binding and ligand-induced structural effect.

Binding affinity is an important factor in drug design to improve drug-target selectivity and specificity. In this study, in silico techniques based on molecular docking followed by molecular dynamics (MD) simulations were utilized to identify the key residue(s) for CSF1R binding affinity among 14 pan-tyrosine kinase inhibitors and 15 CSF1R-specific inhibitors. We found tryptophan at position 550 (W550) on the CSF1R binding site interacted with the inhibitors' aromatic ring in a π-π way that made the ligands better at binding.

-(±)-TTPG-B Attenuates Cell Cycle Progression and Inhibits Cell Proliferation on Cholangiocarcinoma Cells.

This research aimed to determine the target protein and molecular mechanism of -(±)-kusunokinin ((±)-KU) derivatives (-(±)-ARC and -(±)-TTPG-B). Molecular docking was used to predict potential synthesized (±)-KU targets among 22 proteins. The (±)-TTPG-B bound HSP90α better than EC44, native (±)-KU and (-)-KU, and (±)-KU and (-)-ARC.

Extract: Dietary Supplement for Reducing Mammary Tumor Incidence and Chemotherapy-Induced Toxicity.

A low piperine fractional extract (PFPE) was prepared by mixing cold-pressed coconut oil and honey in distilled water, namely, PFPE-CH. In this study, PFPE-CH was orally administered as a dietary supplement to decrease the risk of tumor formation and reduce the side effects of chemotherapeutic drugs during breast cancer treatment. The toxicity study demonstrated no mortality or adverse effects after administrating PFPE-CH at 5000 mg/kg during a 14-day observation period.

-(±)-Kusunokinin Binding to AKR1B1 Inhibits Oxidative Stress and Proteins Involved in Migration in Aggressive Breast Cancer.

Synthetic -(±)-kusunokinin ((±)KU), a potential anticancer substance, was revealed to have an inhibitory effect on breast cancer. According to the computational modeling prediction, AKR1B1, an oxidative stress and cancer migration protein, could be a target protein of -(-)-kusunokinin. In this study, we determined the binding of (±)KU and AKR1B1 on triple-negative breast and non-serous ovarian cancers.

Anticancer Activity of (±)-Kusunokinin Derivatives towards Cholangiocarcinoma Cells.

This study aimed to investigate the cytotoxicity and anticancer activity of (±)-kusunokinin derivatives ((±)-TTPG-A and (±)-TTPG-B). The cytotoxicity effect was performed on human cancer cells, including breast cancer, cholangiocarcinoma, colon and ovarian cancer-cells, compared with normal cells, using the MTT assay. Cell-cycle arrest and apoptosis were detected using flow-cytometry analysis.

Potential Stereoselective Binding of -(±)-Kusunokinin and -(±)-Kusunokinin Isomers to CSF1R.

Breast cancer cell proliferation and migration are inhibited by naturally extracted -(-)-kusunokinin. However, three additional enantiomers of kusunokinin have yet to be investigated: -(+)-kusunokinin, -(-)-isomer and -(+)-isomer. According to the results of molecular docking studies of kusunokinin isomers on 60 breast cancer-related proteins, -(-)-kusunokinin was the most preferable and active component of the -racemic mixture.

Anticancer Effects and Molecular Action of 7-α-Hydroxyfrullanolide in G2/M-Phase Arrest and Apoptosis in Triple Negative Breast Cancer Cells.

Triple negative breast cancer (TNBC) is a breast cancer subtype characterized by the absence of estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 expression. TNBC cells respond poorly to targeted chemotherapies currently in use and the mortality rate of TNBC remains high. Therefore, it is necessary to identify new chemotherapeutic agents for TNBC.

Effects of trans-(±)-kusunokinin on chemosensitive and chemoresistant ovarian cancer cells.

Ovarian cancer ranks eighth in cancer incidence and mortality among women worldwide. Cisplatin-based chemotherapy is commonly used for patients with ovarian cancer. However, the clinical efficacy of cisplatin is limited due to the occurrence of adverse side effects and development of cancer chemoresistance during treatment.

The attenuation effect of low piperine extract on doxorubicin-induced toxicity of blood chemical and immunological properties in mammary tumour rats.

Context: Many natural extracts have been shown to minimize the toxicity of doxorubicin (Dox). Low piperine L. (Piperaceae) extract (PFPE) is a natural extract containing many types of antioxidants that may reduce Dox toxicities.

Trans-(-)-Kusunokinin: A Potential Anticancer Lignan Compound against HER2 in Breast Cancer Cell Lines?

Trans-(-)-kusunokinin, an anticancer compound, binds CSF1R with low affinity in breast cancer cells. Therefore, finding an additional possible target of trans-(-)-kusunokinin remains of importance for further development. Here, a computational study was completed followed by indirect proof of specific target proteins using small interfering RNA (siRNA).

Low Piperine Fractional Piper nigrum Extract Enhanced the Antitumor Immunity via Regulating the Th1/Th2/Treg Cell Subsets on NMU-Induced Tumorigenesis Rats.

Cancer is one of the major causes of death worldwide. In addition to standard regimens, tumor suppression ability has been demonstrated in many types of natural products, including , or black pepper. In previous reports, we demonstrated the antitumor effect of low piperine fractional extract and .

(-)-Kusunokinin as a Potential Aldose Reductase Inhibitor: Equivalency Observed via AKR1B1 Dynamics Simulation.

(-)-Kusunokinin performed its anticancer potency through CFS1R and AKT pathways. Its ambiguous binding target has, however, hindered the next development phase. Our study thus applied molecular docking and molecular dynamics simulation to predict the protein target from the pathways.

(-)-Kusunokinin inhibits breast cancer in N-nitrosomethylurea-induced mammary tumor rats.

Natural and synthetic (-)-kusunokinin inhibited breast cancer, colon cancer and cholangiocarcinoma cells at the G2/M phase and induced apoptosis. However, there is no report on the action and adverse effects of (-)-kusunokinin in animal models. In this study, we investigated the cytotoxic effect of (-)-kusunokinin from Piper nigrum on cancer cells.

Inhibition of CSF1R and AKT by (±)-kusunokinin hinders breast cancer cell proliferation.

Kusunokinin, a lignan compound, inhibits cancer cell proliferation and induces apoptosis; however, the role of kusunokinin is not fully understood. Here, we aimed to identify a target protein of (-)-kusunokinin and determine the protein levels of its downstream molecules. We found that (-)-kusunokinin bound 5 possible target proteins, including CSF1R, MMP-12, HSP90-α, CyclinB1 and MEK1 with ΔG less than -10.

Anticancer activity of synthetic (±)-kusunokinin and its derivative (±)-bursehernin on human cancer cell lines.

Kusunokinin is a potent lignan compound with a several biological properties including antitrypanosomal and anticancer. In this study, (±)-kusunokinin and its derivative, (±)-bursehernin, were synthesized and investigated for their anticancer activities on cell viability, cell cycle arrest and apoptosis in cancer cell lines including breast cancer (MCF-7, MDA-MB-468 and MDA-MB-231), colon cancer (HT-29) and cholangiocarcinoma (KKU-K100, KKU-M213 and KKU-M055) cells. The result showed that (±)-kusunokinin and (±)-bursehernin represented the strongest growth inhibition against breast cancer (MCF-7) and cholangiocarcinoma (KKU-M213) cells with the IC values of 4.

Anti-breast cancer potential of frullanolide from plant by inducing apoptosis.

Breast cancer is the leading cause of female mortality worldwide. Although there are several modern treatments for breast cancer, there is a high rate of recurrence for the majority of treatments; therefore, the search for effective anticancer agents continues. The present study aimed to investigate the anti-breast cancer potential of frullanolide, a compound which is isolated and purified from the plant, for selected human breast cancer cell lines (MCF-7, MDA-MB-468 and MDA-MB-231).

Novel Compound Heterozygous Mutations in the Gene in Two Siblings With Autism and Intellectual Disability.

Autism spectrum disorder (ASD) is a highly heterogeneous neurodevelopmental disorder with many contributing risk genes and loci. To date, several intellectual disability (ID) susceptibility genes have frequently been identified in ASD. Here, whole exome sequencing was carried out on a proband with ASD and identified compound heterozygous mutations of the , which plays a role in the neuronal NF-κB signaling pathway.

Enhanced Oral Bioavailability of Curcumin Using a Supersaturatable Self-Microemulsifying System Incorporating a Hydrophilic Polymer; In Vitro and In Vivo Investigations.

A supersaturatable self-microemulsifying drug delivery system (S-SMEDDS) with a reduced amount of surfactant and incorporation of a polymer precipitation inhibitor, Eudragit® E PO was developed. The optimized S-SMEDDS formulation (SS-15) consisted of 55% surfactants, 40% oils, and 5% Eudragit® E PO (curcumin at 44.4 mg/g of the formulation).

(-)-Kusunokinin and piperloguminine from Piper nigrum: An alternative option to treat breast cancer.

Several studies have reported that active compounds isolated from Piper nigrum possess anticancer properties. However, there are no data on anticancer activity of (-)-kusunokinin and piperlonguminine. The purposes of this study were to isolate active compounds from P.

Structure-guided cancer blockade between bioactive bursehernin and proteins: Molecular docking and molecular dynamics study.

Bursehernin (5'-desmethoxyyatein) is a natural lignan, which has anti-tumor activity in vitro. In this study, the binding-inhibitory effects of bursehernin were screening on selected 80 proteins associated with cancer pathway. The computational analysis suggested inhibitory effect due to bursehernin towards proteins related to cancer proliferation, including FMS kinase receptor, heat shock protein 90-α (Hsp90-α), adenylate cyclase 10 (ADCY10), mitogen-activated protein kinase kinase (MEK1), and α-tubulin.

Senescence Process in Primary Wilms' Tumor Cell Culture Induced by p53 Independent p21 Expression.

Unlabelled: Wilms tumor (WT) is an embryonal tumor occurring in developing kidney tissue. WT cells showing invasive cancer characteristics, also retain renal stem cell behaviours. In-vitro culture of WT is hampered by limited replicative potential.

5,7,4'-Trihydroxy-6,8-diprenylisoflavone and lupalbigenin, active components of Derris scandens, induce cell death on breast cancer cell lines.

Background: Natural products are a potential source for cancer chemotherapeutic development. This current study was performed to investigate the anti-tumor potential of 5,7,4'-trihydroxy-6,8-diprenylisoflavone (TD) and lupalbigenin (LB), plant flavonoids found in Derris scandens Benth (family: Leguminosae), in cancer and normal cell lines.

Methods: The human breast cancer cell lines MCF-7, MDA-MB-231 and MDA-MB-468, the human colon cancer cell line SW-620, and the mouse fibroblast cell line L-929 were used to test their anti-cancer activity.

Anti-cancer effects of Piper nigrum via inducing multiple molecular signaling in vivo and in vitro.

Ethnopharmacological Relevance: Piper nigrum is widely used as a folk medicine including usage for pain relief, fevers, as well as an anti-cancer agent. However the crude extract of piperine free P. nigrum (PFPE), which inhibits breast cancer, and its mechanisms are still being kept secret.

Influence of surfactants in self-microemulsifying formulations on enhancing oral bioavailability of oxyresveratrol: Studies in Caco-2 cells and in vivo.

Self-microemulsifying drug delivery systems (SMEDDS) containing two types (Tween80 and Labrasol) and two levels (low; 5% and high; 15%) of co-surfactants were formulated to evaluate the impact of surfactant phase on physical properties and oral absorption of oxyresveratrol (OXY). All formulations showed a very rapid release in the simulated gastric fluid (SGF) pH 1.2.

Anticancer and Cancer Prevention Effects of Piperine-Free Piper nigrum Extract on N-nitrosomethylurea-Induced Mammary Tumorigenesis in Rats.

Piper nigrum (P. nigrum) is commonly used in traditional medicine. This current study aimed to investigate the anticancer and cancer preventive activity of a piperine-free P.