Fenbendazole and Diisopropylamine Dichloroacetate Exert Synergistic Anti-cancer Effects by Inducing Apoptosis and Arresting the Cell Cycle in A549 Lung Cancer Cells

Article

Author: Nguyen, Son H ; Nguyen, Thai Q ; Nguyen, Dang H ; Hoang, Ba X ; Tran, Phuong T T ; Phan, Uyen T T ; LE, Huong T ; Nguyen, Jolie ; Han, B O

BACKGROUND/AIMLung cancer is the leading cause of cancer-related mortality worldwide, accounting for approximately 2 million new cases and 1.8 million deaths annually. Standard treatment options include surgery, radiation therapy, chemotherapy, and targeted therapies. Despite advancements over the past 25 years, the prognosis of patients with lung cancer remains poor. This study evaluated the synergistic anticancer effects of fenbendazole (FZ) and diisopropylamine dichloroacetate (DADA) on A549 lung cancer cells.MATERIALS AND METHODSFenbendazole (methyl N-(6-phenylsulfanyl-1H-benzimidazol-2-yl) carbamate) is a broad-spectrum benzimidazole anthelmintic commonly used in veterinary medicine. Diisopropylamine Dichloroacetate (DADA), an over-the-counter treatment for chronic liver disease, has demonstrated anti-tumor properties as an inhibitor of pyruvate dehydrogenase kinase.RESULTSThe combination of FZ and DADA exhibited a synergistic effect on inhibiting the proliferation of A549 lung cancer cells. After 48 h of treatment, the FZ-DADA combination produced reactive oxygen species (ROS) and promoted apoptosis by down-regulating Bcl2 and up-regulating BAX protein expression. The combination activated caspase-3, caspase-7, and PARP, further driving apoptosis in A549 cells. The FZ-DADA treatment also induced cell cycle arrest, as evidenced by the inhibition of Cyclin A and Cyclin E proteins.CONCLUSIONThe synergistic anticancer effects of the FZ-DADA combination were confirmed at both cellular and protein levels in A549 lung cancer cells. The combination modulates key apoptotic proteins, induces cell cycle arrest, and increases mitochondrial ROS production, suggesting a promising approach for lung cancer treatment that warrants further investigation and development.

01 Mar 2024·Inflammation Research

Anemoside B4, a new pyruvate carboxylase inhibitor, alleviates colitis by reprogramming macrophage function

Article

Author: Jiang, Hong-Lv ; Chen, Zhong ; Xiao, Ming-Yue ; Ji, Shi-Liang ; Liang, Qing-Hua ; Lin, Yu ; Wang, Ke-Xin ; Liu, Yan-Li ; Li, Qiu-Rong ; Tu, Peng-Fei ; Xu, Guo-Qiang ; Lv, Li-Juan ; Deng, Ke-Jun ; Yang, Shi-Lin ; Gao, Hong-Wei ; Xu, Qiong-Ming ; Zhang, Li ; Kang, Nai-Xin ; Ge, Fei ; Li, Kun

OBJECTIVESColitis is a global disease usually accompanied by intestinal epithelial damage and intestinal inflammation, and an increasing number of studies have found natural products to be highly effective in treating colitis. Anemoside B4 (AB4), an abundant saponin isolated from Pulsatilla chinensis (Bunge), which was found to have strong anti-inflammatory activity. However, the exact molecular mechanisms and direct targets of AB4 in the treatment of colitis remain to be discovered.METHODSThe anti-inflammatory activities of AB4 were verified in LPS-induced cell models and 2, 4, 6-trinitrobenzene sulfonic (TNBS) or dextran sulfate sodium (DSS)-induced colitis mice and rat models. The molecular target of AB4 was identified by affinity chromatography analysis using chemical probes derived from AB4. Experiments including proteomics, molecular docking, biotin pull-down, surface plasmon resonance (SPR), and cellular thermal shift assay (CETSA) were used to confirm the binding of AB4 to its molecular target. Overexpression of pyruvate carboxylase (PC) and PC agonist were used to study the effects of PC on the anti-inflammatory and metabolic regulation of AB4 in vitro and in vivo.RESULTSAB4 not only significantly inhibited LPS-induced NF-κB activation and increased ROS levels in THP-1 cells, but also suppressed TNBS/DSS-induced colonic inflammation in mice and rats. The molecular target of AB4 was identified as PC, a key enzyme related to fatty acid, amino acid and tricarboxylic acid (TCA) cycle. We next demonstrated that AB4 specifically bound to the His879 site of PC and altered the protein's spatial conformation, thereby affecting the enzymatic activity of PC. LPS activated NF-κB pathway and increased PC activity, which caused metabolic reprogramming, while AB4 reversed this phenomenon by inhibiting the PC activity. In vivo studies showed that diisopropylamine dichloroacetate (DADA), a PC agonist, eliminated the therapeutic effects of AB4 by changing the metabolic rearrangement of intestinal tissues in colitis mice.CONCLUSIONWe identified PC as a direct cellular target of AB4 in the modulation of inflammation, especially colitis. Moreover, PC/pyruvate metabolism/NF-κB is crucial for LPS-driven inflammation and oxidative stress. These findings shed more light on the possibilities of PC as a potential new target for treating colitis.

04 Oct 2023·ACS applied materials & interfaces

Synergistic Surface Defect Passivation of Ionic Liquids for Efficient and Stable MAPbI₃-Based Inverted Perovskite Solar Cells.

Article

Author: Silva, S Ravi P ; Sun, Qing ; Shen, Bo ; Hu, Die ; Kang, Bonan ; Liu, Gang ; Deng, Jianguo ; Duan, Shaocong ; Meng, Xiangxin

Organic-inorganic hybrid perovskite solar cells are fabricated using polycrystalline perovskite thin films, which possess high densities of point and surface defects. The surface defects of perovskite thin films are the key factors that affect the device performance. Therefore, the reduction of harmful defects is the primary task for improving device performance. Therefore, in this study, high-quality perovskite thin films are prepared using an ionic liquid, dithiocarbamate diethylamine (DADA), to passivate the interface. The electron-rich sulfur atom in the DADA molecule chelates with the uncoordinated lead ion in the perovskite films, and the diethylammonium cation forms a hydrogen bond with the free iodine ion, which further improves the passivation. The synergistic passivation and improved morphology of the perovskite thin films substantially reduce the number of charged defects on the film surface and prolong the carrier lifetime. In addition, the DADA surface treatment increases the work function of the perovskite film, which is beneficial for carrier transport. Under standard solar-lighting conditions, the power conversion efficiency (PCE) of the device increases from 19.13 to 21.36%, and the fill factor is as high as 83.17%. Owing to both the hydrophobicity of DADA molecules and the passivation of ion defects, the PCE of the device remains above 80%, even for the device stored for 500 h in air at a relative humidity of 65%, and the device stability is substantially improved.

100 Deals associated with Diisopropylamine Dichloroacetate

External Link

KEGG	Wiki	ATC	Drug Bank
-	-	A05A	-

R&D Status

10 top approved records.

to view more data

Indication	Country/Location	Organization	Date
Chronic liver disease	CN	Dan Dong Yi Chuang Yao Ye You Xian Ze Ren Gong Si	-

Clinical Result

Indication

Phase

Evaluation

View All Results

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis