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
-
Diverse Mechanisms of AKT Pathway Activation in Human Malignancy
Current Cancer Drug Targets Is Fast Food Addictive?
Current Drug Abuse Reviews Natural Molecules as Talented Inhibitors of Nucleotide Pyrophosphatases/ Phosphodiesterases (PDEs)
Current Topics in Medicinal Chemistry Novel Nanocolloidal Carriers for Noninvasive Vaccine Delivery
Current Drug Therapy Drugs Interfering with Apoptosis in Breast Cancer
Current Pharmaceutical Design Inflammatory and Non-Inflammatory Roles for Toll-Like Receptors in Gastrointestinal Cancer
Current Pharmaceutical Design Sp/KLF Family and Tumor Angiogenesis in Pancreatic Cancer
Current Pharmaceutical Design Molecular Farming of Pharmaceutical Proteins Using Plant Suspension Cell and Tissue Cultures
Current Pharmaceutical Design Determination of the Sodium Concentration in Brazilian Light and Non- Light Powdered Instant Soups by Flame Photometry
Current Nutrition & Food Science Furanodienone: An Emerging Bioactive Furanosesquiterpenoid
Current Organic Chemistry Patent Selections
Recent Patents on Anti-Cancer Drug Discovery Synthesis and Evaluation of Anti-inflammatory and Analgesic Activities of New 1,2,4-triazole Derivatives
Medicinal Chemistry Novel Antibody Therapeutics Targeting Mesothelin In Solid Tumors
Clinical Cancer Drugs Potentials of Polymeric Nanoparticle as Drug Carrier for Cancer Therapy: With a Special Reference to Pharmacokinetic Parameters
Current Drug Metabolism Selective Internal Radiation Therapy with Yttrium-90 for Unresectable Liver Tumours
Reviews on Recent Clinical Trials Inhibitory Potential of Dietary Nutraceuticals on Cellular PI3K/Akt Signaling: Implications in Cancer Prevention and Therapy
Current Topics in Medicinal Chemistry Based on Nucleotides Analysis of Tumor Cell Lines to Construct and Validate a Prediction Model of Mechanisms of Chemotherapeutics
Anti-Cancer Agents in Medicinal Chemistry Cancer Gene Therapy with Tissue Inhibitors of Metalloproteinases (TIMPs)
Current Gene Therapy Vitamin D Receptor Signaling and Pancreatic Cancer Cell EMT
Current Pharmaceutical Design Targeting Cyclooxygenase-2 in Hematological Malignancies: Rationale and Promise
Current Pharmaceutical Design