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
-
Regulation of Gene Expression by Progesterone in Cancer Cells: Effects on Cyclin D1, EGFR and VEGF
Mini-Reviews in Medicinal Chemistry Retinoid Related Molecules an Emerging Class of Apoptotic Agents with Promising Therapeutic Potential in Oncology: Pharmacological Activity and Mechanisms of Action
Current Pharmaceutical Design Current and Future Prospective of a Versatile Moiety: Imidazole
Current Drug Targets Anticancer Antifolates: Current Status and Future Directions
Current Pharmaceutical Design Lycopene Modulation of Molecular Targets Affected by Smoking Exposure
Current Cancer Drug Targets Isoprenylation of Intracellular Proteins as a New Target for the Therapy of Human Neoplasms: Preclinical and Clinical Implications
Current Drug Targets Tumor Control by Manipulation of the Human Anti-Apoptotic Survivin Gene
Current Cancer Therapy Reviews Anti-Inflammatory, Gastrointestinal and Hepatoprotective Effects of Ocimum sanctum Linn: An Ancient Remedy with New Application
Inflammation & Allergy - Drug Targets (Discontinued) The JNK Signaling Pathway Is a Novel Molecular Target for S-Propargyl- L-Cysteine, a Naturally-Occurring Garlic Derivatives: Link to Its Anticancer Activity in Pancreatic Cancer In Vitro and In Vivo
Current Cancer Drug Targets Probiotics as an Alternative Strategy for Prevention and Treatment of Human Diseases: A Review
Inflammation & Allergy - Drug Targets (Discontinued) Potential Applications of Induced Pluripotent Stem Cells (iPSCs) in the Modeling of Gastrointestinal Disorders
Current Stem Cell Research & Therapy Recent Developments in Chimeric NSAIDs as Anticancer Agents: Teaching an Old Dog a New Trick
Mini-Reviews in Medicinal Chemistry Molecular Mechanism of the Canonical Oncogenic lncRNA MALAT1 in Gastric Cancer
Current Medicinal Chemistry Prospectives of Antihypertensive Nano-ceuticals as Alternative Therapeutics
Current Drug Targets Induction of Abscopal Anti-Tumor Immunity and Immunogenic Tumor Cell Death by Ionizing Irradiation - Implications for Cancer Therapies
Current Medicinal Chemistry Critical Role of Hypoxia Sensor - HIF-1α in VEGF Gene Activation. Implications for Angiogenesis and Tissue Injury Healing
Current Medicinal Chemistry Emerging Role of Circular RNAs in Kidney Diseases in Nephrology
Current Drug Targets Compounds from Wild Mushrooms with Antitumor Potential
Anti-Cancer Agents in Medicinal Chemistry MicroRNAs Patents: The Road From Bench to Bedsides for Cancer Treatment
Recent Patents on DNA & Gene Sequences Transmembrane Phosphatases and Cancer Development, the Role of Protein Tyrosine Phosphatase-kappa (PTPκ) and Protein Tyrosine Phosphatase-mu (PTPμ)
Current Signal Transduction Therapy