Abstract
Background: Recognition of a new therapeutic agent may activate an alternative programmed cell death for the treatment of breast cancer.
Objective: Here, it has been tried to evaluate the effects of Shikonin, a naphthoquinone derivative of Lithospermum erythrorhizon, on the induction of necroptosis and apoptosis mediated by RIPK1-RIPK3 in the ER+ breast cancer cell line, MCF-7.
Methods: In the current study, cell death modalities, cell cycle patterns, RIPK1 and RIPK3 expressions, caspase-3 and caspase-8 activities, reactive oxygen species and mitochondrial membrane potential have been evaluated in the Shikonin-treated MCF-7 cells.
Results: Necroptosis and apoptosis have been occurred by Shikonin, with a significant increase in RIPK1 and RIPK3 expressions, although necroptosis was the major rout in MCF-7 cells. Shikonin significantly increased the percentage of the cells in sub-G1 and also those in the later stages of cell cycle, which represents an increase in necroptosis and apoptosis. Under caspase inhibition by Z-VAD-FMK, Shikonin has stimulated necroptosis, which could be arrested by Nec-1. An increase in ROS levels and a decrease in the mitochondrial membrane potential have also been observed.
Conclusion: On the basis of present findings, Shikonin has been suggested as a good candidate for the induction of cell death in ER+ breast cancer, although further investigations, experimental and clinical, are required.
Keywords: Shikonin, Necroptosis, Apoptosis, ROS, Estrogen receptor positive, MCF-7.
Anti-Cancer Agents in Medicinal Chemistry
Title:Targeting Cell Necroptosis and Apoptosis Induced by Shikonin via Receptor Interacting Protein Kinases in Estrogen Receptor Positive Breast Cancer Cell Line, MCF-7
Volume: 18 Issue: 2
Author(s): Zahra Shahsavari, Fatemeh Karami-Tehrani* Siamak Salami
Affiliation:
- Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran,Iran
Keywords: Shikonin, Necroptosis, Apoptosis, ROS, Estrogen receptor positive, MCF-7.
Abstract: Background: Recognition of a new therapeutic agent may activate an alternative programmed cell death for the treatment of breast cancer.
Objective: Here, it has been tried to evaluate the effects of Shikonin, a naphthoquinone derivative of Lithospermum erythrorhizon, on the induction of necroptosis and apoptosis mediated by RIPK1-RIPK3 in the ER+ breast cancer cell line, MCF-7.
Methods: In the current study, cell death modalities, cell cycle patterns, RIPK1 and RIPK3 expressions, caspase-3 and caspase-8 activities, reactive oxygen species and mitochondrial membrane potential have been evaluated in the Shikonin-treated MCF-7 cells.
Results: Necroptosis and apoptosis have been occurred by Shikonin, with a significant increase in RIPK1 and RIPK3 expressions, although necroptosis was the major rout in MCF-7 cells. Shikonin significantly increased the percentage of the cells in sub-G1 and also those in the later stages of cell cycle, which represents an increase in necroptosis and apoptosis. Under caspase inhibition by Z-VAD-FMK, Shikonin has stimulated necroptosis, which could be arrested by Nec-1. An increase in ROS levels and a decrease in the mitochondrial membrane potential have also been observed.
Conclusion: On the basis of present findings, Shikonin has been suggested as a good candidate for the induction of cell death in ER+ breast cancer, although further investigations, experimental and clinical, are required.
Export Options
About this article
Cite this article as:
Shahsavari Zahra , Karami-Tehrani Fatemeh *, Salami Siamak, Targeting Cell Necroptosis and Apoptosis Induced by Shikonin via Receptor Interacting Protein Kinases in Estrogen Receptor Positive Breast Cancer Cell Line, MCF-7, Anti-Cancer Agents in Medicinal Chemistry 2018; 18 (2) . https://dx.doi.org/10.2174/1871520617666170919164055
DOI https://dx.doi.org/10.2174/1871520617666170919164055 |
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
-
Agents Targeting Prostate Cancer Bone Metastasis
Anti-Cancer Agents in Medicinal Chemistry Graphical Abstracts:
Current Organic Chemistry HDAC Inhibitors-New Generation of Target Specific Treatment
Mini-Reviews in Medicinal Chemistry Anti-inflammatory Property of AMP-activated Protein Kinase
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Editorial (Thematic Issue: Mitochondrial Biogenesis: Pharmacological Approaches)
Current Pharmaceutical Design ATP-Binding Cassette Efflux Transporters in Human Placenta
Current Pharmaceutical Biotechnology Melatonin and Its Therapeutic Potential in Neuroprotection
Central Nervous System Agents in Medicinal Chemistry Synthesis of Arylamino-1,3,5-triazines Functionalized with Alkylatin 2-chloroethylamine Fragments and Studies of their Cytotoxicity on the Breast Cancer MCF-7 Cell Line
Anti-Cancer Agents in Medicinal Chemistry Lycopene Protects Liver Against Ulcerative Colitis
Current Drug Therapy Phytocannabinoids and Cannabimimetic Drugs: Recent Patents in Central Nervous System Disorders
Recent Patents on CNS Drug Discovery (Discontinued) Bisphosphonates and Cancer: A Relationship Beyond the Antiresorptive Effects
Mini-Reviews in Medicinal Chemistry Synthesis and Biological Evaluation of Pyrazole amides fused Combretastatin Derivatives as Anticancer Agents
Current Bioactive Compounds Molecular Interaction and Computational Analytical Studies of Pinocembrin for its Antiangiogenic Potential Targeting VEGFR-2: A Persuader of Metastasis
Medicinal Chemistry PPARγ and Its Ligands: Potential Antitumor Agents in the Digestive System
Current Stem Cell Research & Therapy The PI3K/AKT/mTOR-Signal Transduction Pathway as Drug Target in Triple-Negative Breast Cancer
Clinical Cancer Drugs Synthesis and Stability Evaluation of New HYNIC Derivatives as Ligands for Technetium-99m
Letters in Organic Chemistry ACO Inspired Computer-aided Detection/Diagnosis (CADe/CADx) Model for Medical Data Classification
Recent Patents on Computer Science Physiopathological Roles of P2X Receptors in the Central Nervous System
Current Medicinal Chemistry Water-Refined Solution Structure of the Human Grb7-SH2 Domain in Complex with the erbB2 Receptor Peptide pY1139
Protein & Peptide Letters Rab GTPases, Membrane Trafficking and Diseases
Current Drug Targets