- Home
- A-Z Publications
- Clinical Cancer Drugs
- Fast Track Listing
Clinical Cancer Drugs - Online First
Description text for Online First listing goes here...
-
-
PROTAC and PROTAB: Revolutionizing Cancer Therapy by Targeted Protein Degradation
Authors: Swati Verma, Sarvesh Paliwal and Debashish ParamanickAvailable online: 15 November 2024More LessChemotherapeutic strategies that target irregularly produced or mutant proteins using monoclonal antibodies (mAbs) and tiny molecular inhibitors have been extensively employed to target cancer. However, because most intracellular proteins lack antigens or active sites with which mAbs or SMIs can engage, they have not been considered druggable targets. After extensive research, PROTACs (Proteolysis Targeting chimaeras) have become a promising way to work with proteins. Scaffolding proteins and transcription factors may also be targeted. The present targets of PROTACs include kinases like CDKs and RTKs, overexpressed oncogenic proteins like AR and BRDs, cancer-driven mutant proteins like EGFR, and disease-relevant fusion proteins like NPM/EML4-ALK and BCR-ABL. The inability of small-molecule intracellular degraders to enter cells and their low bioavailability can also be circumvented with PROTABs. The use of multispecific binding proteins is an improved way to target the breakdown of membrane-bound and cell-surface proteins.
-
-
-
Synergistic Action of Thymol-citral is Associated with Cell Cycle Arrest and Intracellular ROS Generation in A549 Cells
Available online: 24 October 2024More LessObjectiveNSCLC is the predominant form of lung cancer, often exhibiting resistance to chemotherapy. Thymol and citral have shown promise as anticancer agents in different cancer cell lines but have not been evaluated in combination against NSCLC. Hence, we planned to investigate the anticancer effect of thymol-citral combination and explore its mechanisms of action against A549 cells.
MethodsA549 cells were exposed to varying concentrations of thymol and citral, alone and in combination. Cell proliferation, plasma membrane integrity, apoptotic markers, reactive oxygen species (ROS) levels, cell cycle distribution, senescence induction, and migration potential were assessed. Additionally, in vitro safety was evaluated in human bronchial epithelial cells (HBECs) and human red blood cells (RBCs).
ResultsThymol and citral showed synergistic action against A549 cells, with a CI value of 0.75. After 24 h, they induced apoptosis, caused G0/G1 phase arrest, and increased ROS levels, suggesting oxidative stress as the mechanism. This combination also induced cell senescence, significantly inhibited A549 cell migration, and was non-toxic to human RBCs and HBECs.
ConclusionOverall, the thymol-citral synergistic combination was found to be a safe and effective therapy option for non-small cell lung cancer.
-
-
-
PNU-74654 Enhanced the Antiproliferative Activity of Gemcitabine by Targeting Wnt/β-Catenin Pathway in Pancreatic Cancer
Available online: 21 October 2024More LessBackgroundThe Wnt/beta-catenin pathway is one of the pathways that is deregulated in pancreatic cancer and is reported to be associated with a poor prognosis. This indicates the need for the identification of novel agents to improve the efficacy of current therapy or have an improved efficacy. Therefore, in the present study, we explored the anticancer activity of PNU-74654 alone or in combination with gemcitabine in 2 and 3-dimensional cell culture models of pancreatic cancer.
MethodsThe MTT assay was carried out to determine the viability of PC cancerous cells (PCCs), while the cytotoxicity of this agent was evaluated in a 3D cell culture model (spheroid). The effects of PNU-74654 were investigated in established cell migration/invasion assays.
ResultsThe expression of candidate genes affecting the cell cycle, migration, and Wnt/b-catenin pathway was evaluated at mRNA and/or proteins by RT-PCR or Western blot. PNU-74654 inhibited the cell growth at IC50 of 122 ± 0.4 umol/L and had a synergistic effect on the antiproliferative properties of gemcitabine by modulating the Wnt pathway. The PNU-74654/gemcitabine combination reduced the migratory and invasiveness of PC cells, compared to control cells, through perturbation of E-cadherin.
ConclusionOur findings demonstrate the profound antitumor properties of PNU-74654 in in vitro models of pancreatic cancer, supporting further in vivo studies to evaluate the therapeutic impact of this novel therapy to target the Wnt pathway in the treatment of pancreatic cancer.
-