The Pim-1 kinase regulates cell survival, proliferation, and differentiation and is overexpressed frequently in many malignancies, including leukemia and skin cancer. In this study, we used kinase profiling analysis to demonstrate that 2'-hydroxycinnamicaldehyde (2'-HCA), a compound found in cinnamon, specifically inhibits Pim-1 activity. Cocrystallography studies determined the hydrogen bonding pattern between 2'-HCA and Pim-1. Notably, 2'-HCA binding altered the apo kinase structure in a manner that shielded the ligand from solvent, thereby acting as a gatekeeper loop. Biologically, 2'-HCA inhibited the growth of human erythroleukemia or squamous epidermoid carcinoma cells by inducing apoptosis. The compound was also effective as a chemopreventive agent against EGF-mediated neoplastic transformation. Finally, 2'-HCA potently suppressed the growth of mouse xenografts representing human leukemia or skin cancer. Overall, our results offered preclinical proof of concept for 2'-HCA as a potent anticancer principle arising from direct targeting of the Pim-1 kinase.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4490130 | PMC |
| http://dx.doi.org/10.1158/0008-5472.CAN-14-3655 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Amyotrophic lateral sclerosis in a patient with chronic lymphocytic leukaemia and drug related sarcoid-like reaction.
BMC Neurol
January 2025
Department of Neurology, Wessex Neurological Centre, University Hospital Southampton, Southampton, UK.
Article Synopsis
- Sarcoid-like reaction (SLR) is an immune response affecting lymph nodes and organs, which doesn't fulfill the criteria for systemic sarcoidosis, and can be associated with certain diseases like Chronic lymphocytic leukaemia (CLL) and Amyotrophic lateral sclerosis (ALS).
- A 60-year-old male patient with treated CLL developed ALS symptoms following exposure to Venetoclax and Rituximab, presenting with rashes and weakness that progressed over a year.
- Diagnosis complications included atypical signs and symptoms, leading to misdiagnosis of neurosarcoidosis and challenges in treatment, despite initial interventions with prednisolone and infliximab.
A case of pityriasis rubra pilaris secondary to ponatinib.
SAGE Open Med Case Rep
January 2025
Departement of Dermatology, Charles-Le Moyne Hospital, Longueuil, QC, Canada.
Ponatinib, a tyrosine kinase inhibitor used for chronic myeloid leukemia and acute lymphoblastic leukemia, can cause rare cutaneous side effects. In this case, a 63-year-old woman developed a pityriasis rubra pilaris-like eruption 1 month after starting the drug. The skin reaction improved with dose reduction and recurred more mildly at a lower dose.
View Article and Find Full Text PDFTalquetamab plus Teclistamab in Relapsed or Refractory Multiple Myeloma.
N Engl J Med
January 2025
From Tel Aviv Sourasky Medical Center (Y.C.C., I.A.), and the Faculty of Medical and Health Sciences, Tel Aviv University (Y.C.C., H.M., I.A.), Tel Aviv, Chaim Sheba Medical Center, Ramat Gan (H.M.), and Hadassah Hebrew University Medical Center, Jerusalem (M.G.) - all in Israel; McGill University and McGill University Health Centre, Montreal (M.S.), and Alberta Health Services, Edmonton (M.P.C.) - all in Canada; Samsung Medical Center, Sungkyunkwan University School of Medicine (K.K.), Seoul St. Mary's Hospital, Catholic University of Korea (C.-K.M.), and Seoul National University College of Medicine (S.-S.Y.) - all in Seoul, South Korea; Hospital Universitario Marqués de Valdecilla, Instituto de Investigación Sanitaria Valdecilla, Universidad de Cantabria, Santander (E.M.O.), Cancer Center Clínica Universidad de Navarra, Center for Applied Medical Research, Pamplona (P.R.-O.), Institut Català d'Oncologia, Josep Carreras Leukemia Research Institute, and the Hospital Germans Trias i Pujol, Barcelona (A.O.), START Madrid-Fundación Jiménez Díaz Early Phase Unit, University Hospital Fundación Jiménez Díaz, Madrid (D.M.), and the University Hospital of Salamanca, Institute for Biomedical Research of Salamanca, the Salamanca Cancer Research Center, and Centro de Investígación Biomédica en Red Cáncer, Salamanca (M.-V.M.) - all in Spain; Janssen Research and Development, Spring House, PA (N.A.Q.C., A.K., M.K., M.R.P., E.S., B.H., J.V., A.B.); and Janssen Research and Development, Allschwil, Switzerland (L.D.S.).
Background: Talquetamab (anti-G protein-coupled receptor family C group 5 member D) and teclistamab (anti-B-cell maturation antigen) are bispecific antibodies that activate T cells by targeting CD3 and that have been approved for the treatment of triple-class-exposed relapsed or refractory multiple myeloma.
Methods: We conducted a phase 1b-2 study of talquetamab plus teclistamab in patients with relapsed or refractory multiple myeloma. In phase 1, we investigated five dose levels in a dose-escalation study.
JAGN1 (Jagunal-homolog1) is a ER-resident transmembrane protein which is part of the early secretory pathway and granulocyte colony-stimulating factor receptor mediated signaling. Autosomal recessively inherited variants in the JAGN1 gene lead to congenital neutropenia, early-onset bacterial infections, aphthosis and skin abscesses due to aberrant differentiation and maturation of neutrophils. In addition, bone metabolism disorders and a syndromic phenotype, including facial features, short stature and neurodevelopmental delay, have been reported in affected patients.
View Article and Find Full Text PDFEvaluation of QuantiFERON-TB Gold for the Diagnosis of Infection in HTLV-1-Infected Patients.
Viruses
November 2024
Laboratório Avançado de Saúde Pública, Instituto Gonçalo Moniz, Fundação Oswaldo Cruz (Fiocruz-BA), Salvador 40296-710, Bahia, Brazil.
Human T-cell leukemia virus type 1 (HTLV-1) is associated with an increased risk of tuberculosis (TB). This study aimed to evaluate the performance of the QuantiFERON-TB Gold (QFT) test for the diagnosis of (MTB) infection in HTLV-1-infected individuals. HTLV-1-infected participants were divided into four groups: HTLV-1-infected individuals with a history of tuberculosis (HTLV/TB), individuals with positive HTLV and tuberculin skin tests (HTLV/TST+) or negative TST (HTLV/TST-), and HTLV-1-negative individuals with positive TST results (HN/TST+).
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!