Abstract
The newly synthesized naftopidil analogue HUHS1015 reduced viability of MKN28 and MKN45 human gastric cancer cells in a concentration (0.3-100 μM)-dependent manner, with the potential greater than that for naftopidil. In the cell cycle analysis, HUHS1015 significantly increased the proportion at the subG1 phase of cell cycling in MKN28 cells. In the flow cytometry using propidium iodide (PI) and annexin V, HUHS1015 significantly increased the populations of PI-positive/annexin V-negative and PI-positive/annexin V-positive MKN28 cells, corresponding to primary necrosis and late apoptosis/secondary necrosis, respectively. HUHS1015-induced MKN28 cell death was attenuated by the necroptosis inhibitor Nec-1. In the enzymatic caspase assay, caspase-3, -4, -8, and -9 were not sufficiently activated by HUHS1015. HUHS1015 increased nuclear localization of apoptosis-inducing factor-homologous mitochondrion-associated inducer of death (AMID), without affecting expression of the AMID mRNA and protein in MKN28 cells. HUHS1015 caused nuclear fragmentation and condensation in MKN28 cells treated with HUHS1015. Taken together, these results of the present study indicate that HUHS1015 induces both necroptosis and caspase-independent apoptosis of MKN28 cells, possibly the latter effect being due to AMID accumulation in the nucleus.
Keywords: AMID, caspase-independent apoptosis, HUHS1015, MKN28 gastric cancer cell, necroptosis.
Graphical Abstract
Call for Papers in Thematic Issues
Advances in Nanomedicines and Targeted Therapies for Colorectal Cancer
Colorectal cancer remains a significant global health challenge, with high incidence and mortality rates despite advancements in treatment strategies. Conventional therapies often face limitations such as systemic toxicity, drug resistance, and suboptimal targeting. The advent of nanomedicines and innovative drug delivery systems offers new hope for overcoming these challenges and ...read more
Designing Novel Molecules for Anti-Cancer Enzyme Modulation: A Mechanistic and Therapeutic Perspective
The deficiencies or hyper functions of enzymes cause a number of diseases. Enzyme inhibition is an important area of pharmaceutical research since studies in this field have already led to the discovery of wide variety of drugs useful in a number of diseases. Specific inhibitors interact with enzymes and block ...read more
Discovery of Lead compounds targeting transcriptional regulation
Transcriptional regulation plays key physiological functions in body growth and development. Transcriptional dysregulation is one of the important biomarkers of tumor genesis and progression, which is involved in regulating tumor cell processes such as cell proliferation, differentiation, and apoptosis. Additionally, it plays a pivotal role in angiogenesis and promotes tumor ...read more
Heterocyclic Systems: Bridging Chemistry and Biology in Cancer Therapy
The thematic issue, "Heterocyclic Systems: Bridging Chemistry and Biology in Cancer Therapy," explores the critical role of heterocyclic compounds in advancing the frontiers of cancer treatment. Heterocycles serve as fundamental building blocks in medicinal chemistry due to their structural diversity and ability to interact with biological targets. This issue aims ...read more
Related Journals
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry
Current Analytical Chemistry
Current Computer-Aided Drug Design
Current Bioactive Compounds
Current Cancer Drug Targets
Combinatorial Chemistry & High Throughput Screening
Current Cancer Therapy Reviews
Current Diabetes Reviews
Current Drug Safety
Current Drug Targets
Related Books
Organic Spectroscopy Technology and Applications
Andrographolide and its Analogs: Botanical Sources, Phytochemistry, Pharmacology, and Biotechnology
Metabolites of Medicinal Plants: Insightful Approaches
2-Deoxy-D-Glucose: Chemistry and Biology
Chiral Ionic Liquids: Applications in Chemistry and Technology
Anthocyanins: Pharmacology and Nutraceutical Importance
Therapeutic Insights into Herbal Medicine through the Use of Phytomolecules
Computer-Aided Drug Discovery Methods: A Brief Introduction
The Roles and Responsibilities of Clinical Pharmacists in Hospital Settings
Bioactive Compounds from Medicinal Plants for Cancer Therapy and Chemoprevention
44
