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.
Anti-Cancer Agents in Medicinal Chemistry
Title:HUHS1015 Induces Necroptosis and Caspase-Independent Apoptosis of MKN28 Human Gastric Cancer Cells in Association with AMID Accumulation in the Nucleus
Volume: 15 Issue: 2
Author(s): Yoshiko Kaku, Ayako Tsuchiya, Takeshi Kanno and Tomoyuki Nishizaki
Affiliation:
Keywords: AMID, caspase-independent apoptosis, HUHS1015, MKN28 gastric cancer cell, necroptosis.
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.
Export Options
About this article
Cite this article as:
Kaku Yoshiko, Tsuchiya Ayako, Kanno Takeshi and Nishizaki Tomoyuki, HUHS1015 Induces Necroptosis and Caspase-Independent Apoptosis of MKN28 Human Gastric Cancer Cells in Association with AMID Accumulation in the Nucleus, Anti-Cancer Agents in Medicinal Chemistry 2015; 15 (2) . https://dx.doi.org/10.2174/1871520614666140922122700
DOI https://dx.doi.org/10.2174/1871520614666140922122700 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
Call for Papers in Thematic Issues
Induction of cell death in cancer cells by modulating telomerase activity using small molecule drugs
Telomeres are distinctive but short stretches present at the corners of chromosomes and aid in stabilizing chromosomal makeup. Resynthesis of telomeres supported by the activity of reverse transcriptase ribonucleoprotein complex telomerase. There is no any telomerase activity in human somatic cells, but the stem cells and germ cells undergone telomerase ...read more
Role of natural compounds as anti anti-cancer agents
Cancer is considered the leading cause of worldwide mortality, accounting for nearly 10 million deaths in 2022. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy remains an important approach in treatment o f several types of cancers, even though ...read more
Signaling and enzymatic modulators in cancer treatment
Cancer accounts for nearly 10 million deaths in 2022 and is considered the leading cause of worldwide mortality. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy, radiotherapy and surgery are the most important approach for the treatment of several ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Tanshinone IIA Protects Hippocampal Neuronal Cells from Reactive Oxygen Species Through Changes in Autophagy and Activation of Phosphatidylinositol 3-Kinase, Protein Kinas B, and Mechanistic Target of Rapamycin Pathways
Current Neurovascular Research Protein Phosphatase 1 and Its Complexes in Carcinogenesis
Current Cancer Drug Targets Gastroduodenal Disorders in Patients with CVID Undergoing Immunoglobulin Therapy
Current Pharmaceutical Biotechnology Development of PET Probes for Cancer Imaging
Current Topics in Medicinal Chemistry Ginger for Prevention or Treatment of Drug-Induced Nausea and Vomiting
Current Clinical Pharmacology Neuroprotective Effects of Drug-Induced Therapeutic Hypothermia in Central Nervous System Diseases
Current Drug Targets Cancer Proteomics: New Horizons and Insights into Therapeutic Applications
Current Proteomics Biodefense Properties of Milk: The Role of Antimicrobial Proteins and Peptides
Current Pharmaceutical Design Carbohydrate based Potential Chemotherapeutic Agents: Recent Developments and their Scope in Future Drug Discovery
Mini-Reviews in Medicinal Chemistry A Critical Review on Potential Advancements of Nanostructured Lipid Carriers in Drug Delivery
Current Nanomedicine In Vitro Anticancer Evaluation of Some Synthesized 2H-Quinolinone and Halogenated 2H-Quinolinone Derivatives as Therapeutic Agents
Anti-Cancer Agents in Medicinal Chemistry Clinical Uses of Melatonin: Evaluation of Human Trials
Current Medicinal Chemistry The Possible Existence of a Gut-Bone Axis Suggested by Studies of Genetically Manipulated Mouse Models?
Current Pharmaceutical Design Plant-Derived Biomolecules and Drug Delivery Systems in the Treatment of Liver and Kidney Diseases
Current Pharmaceutical Design Quinone-Based Drugs: An Important Class of Molecules in Medicinal Chemistry
Medicinal Chemistry Cisplatin Is a DNA-Damaging Antitumour Compound Triggering Multifactorial Biochemical Responses in Cancer Cells: Importance of Apoptotic Pathways
Current Medicinal Chemistry - Anti-Cancer Agents Temporal Expression of miRNAs in Laser Capture Microdissected Palate Medial Edge Epithelium from Tgfβ3<sup>-/-</sup> Mouse Fetuses
MicroRNA Recent Advances in the Synthesis of 1,3-Azoles
Current Topics in Medicinal Chemistry The Role of cMet in Non-Small Cell Lung Cancer Resistant to EGFRInhibitors: Did We Really Find the Target?
Current Drug Targets Relationship Between Inflammation, Insulin Resistance and Type 2 Diabetes: Cause or Effect?
Current Diabetes Reviews