Isfahan University of Medical Sciences

Science Communicator Platform

Stay connected! Follow us on X network (Twitter):
Share this content! On (X network) By
Α2β1 Integrin Specific Inhibitor Btt-3033 Promotes Paclitaxel-Induced Apoptosis in Human Ovarian Cancer Cells Publisher



Babaei Z1 ; Amani M2 ; Minaiyan M3 ; Ghorbanhosseini SS2 ; Aghaei M2, 4
Authors
Show Affiliations
Authors Affiliations
  1. 1. Department of Clinical Biochemistry and Biophysics, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
  2. 2. Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
  3. 3. Department of Pharmacology and Toxicology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
  4. 4. Isfahan Pharmaceutical Sciences Research Centre, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran

Source: Research in Pharmaceutical Sciences Published:2024


Abstract

Background and purpose: The new plan of using molecular targeted agents in combination with cytotoxic drugs may represent a promising strategy to increase the efficacy of chemotherapy. Hence, we examined whether α2β1 integrin-specific inhibitor, BTT-3033, could modulate the susceptibility of OVCAR3 and SKOV3 ovarian cancer cells to paclitaxel (PTX). Experimental approach: Ovarian cancer cell lines were treated with BTT-3033 and different concentrations of PTX. To determine the mechanisms involved in the PTX/BTT-3033 combination-induced cell death, cell viability, apoptosis, reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP), and caspase-3 activity were evaluated. Findings/Results: Both BTT-3033 (≥ 1 μM) and PTX (≥ 0.01 μM) suppressed the proliferation of OVCAR3 and SKOV3 cells in a concentration-related manner. Pretreatment with BTT-3033 (1 μM), followed by PTX-induced synergistic antiproliferative effects, decreased the IC 50 values of PTX from 0.45 to 0.03 μM in OVCAR3 and 0.35 to 0.02 μM in SKOV3 cells. All of the coefficients of drug interaction for various PTX and BTT-3033 combinations were found to be less than 1. Moreover, PTX/BTT-3033 combination induced more apoptotic cells (from 4.2% to 87.0% in OVCAR3 and 2.4% to 88.5% in SKOV3) than PTX alone. Combination therapy also decreased MMP and increased the caspase-3 activity. Additionally, we found that the PTX/BTT-3033 combination enhanced ROS production in OVCAR3 and SKOV3 cells. Conclusion and implications: BTT-3033 has demonstrated the ability to enhance the susceptibility of ovarian cancer cells to PTX by inducing MMP loss, ROS production, and mitochondrial apoptosis, therefore this combination therapy might represent a promising strategy for ovarian cancer treatment. Copyright © 2024 Research in Pharmaceutical Sciences.
Related Docs
View other Related Docs
1. Jatropha-6(17),11 E -Diene Class Derivatives Induce Apoptosis Effects in Ovcar-3 and Caov-4 Ovarian Cancer Cell Lines Via a Mitochondrial Pathway, Biochemistry and Cell Biology (2017)
2. Sar131675 Exhibits Anticancer Activity on Human Ovarian Cancer Cells Through Inhibition of Vegfr-3/Erk1/2/Akt Signaling Pathway, Cellular Signalling (2023)
3. Sar131675 Receptor Tyrosine Kinase Inhibitor Induces Apoptosis Through Bcl-2/Bax/Cyto C Mitochondrial Pathway in Human Umbilical Vein Endothelial Cells, Anti-Cancer Agents in Medicinal Chemistry (2022)
4. Galectin-9 Induces Apoptosis in Ovcar-3 Ovarian Cancer Cell Through Mitochondrial Pathway, Research in Pharmaceutical Sciences (2018)
5. Adenosine Induces Cell Cycle Arrest and Apoptosis Via Cyclind1/Cdk4 and Bcl-2/Bax Pathways in Human Ovarian Cancer Cell Line Ovcar-3, Tumor Biology (2013)
6. Activation of A2b Adenosine Receptor Regulates Ovarian Cancer Cell Growth: Involvement of Bax/Bcl-2 and Caspase-3, Biochemistry and Cell Biology (2015)
7. In Vitro Evaluation of the Pogostone Effects on the Expression of Pten and Dact1 Tumor Suppressor Genes, Cell Cycle, and Apoptosis in Ovarian Cancer Cell Line, Research in Pharmaceutical Sciences (2022)
8. Dihydroartemisinin Enhances the Therapeutic Efficacy of Bh3 Mimetic Inhibitor in Acute Lymphoblastic Leukemia Cells Via Inhibition of Mcl-1, Asian Pacific Journal of Cancer Prevention (2024)
Experts (# of related papers)
View all Related Experts
Mahmoud Aghaei (19)
Mustafa Ghanadian (6)
Other Related Docs
9. 15-Hydroxy-8(17),13(E)-Labdadiene-19-Carboxylic Acid (Hlca) Inhibits Proliferation and Induces Cell Cycle Arrest and Apoptosis in Ovarian Cancer Cells, Life Sciences (2021)
10. Galectin-9 Inhibits Cell Proliferation and Induces Apoptosis in Jurkat and Ke-37 Acute Lymphoblastic Leukemia Cell Lines Via Caspase-3 Activation, Research in Pharmaceutical Sciences (2021)
11. Persianolide-A, an Eudesmanolide-Type Sesquiterpene Lactone From Artemisia Kopetdaghensis, Induces Apoptosis by Regulating Erk Signaling Pathways, Research in Pharmaceutical Sciences (2024)
12. The Effects of Abt-199 and Dihydroartemisinin Combination on Cell Growth and Apoptosis in Human U937 and Kg-1 Cancer Cells, Asian Pacific Journal of Cancer Prevention (2024)
13. Progesterone Decreases Viability and up Regulates Membrane Progesterone Receptors Expression on the Human Chronic Myeloid Leukemia Cell Line, Cancer Genetics (2024)
14. Pharmacokinetics, Organ Toxicity and Antitumor Activity of Docetaxel Loaded in Folate Targeted Cholesterol Based Micelles, Current Drug Delivery (2016)
15. Hybrid Benzoxazole-Coumarin Compounds Induce Death Receptor-Mediated Switchable Apoptotic and Necroptotic Cell Death on Hn-5 Head and Neck Cancer Cell Line, Anti-Cancer Agents in Medicinal Chemistry (2016)
16. Adenosine Induces Cell-Cycle Arrest and Apoptosis in Androgen-Dependent And-Independent Prostate Cancer Cell Lines, Lncap-Fgc-10, Du-145, and Pc3, Prostate (2012)
17. Atorvastatin Enhances Anti-Apoptotic Effects of Tamoxifen on Melanoma Cancer Cells, Bratislava Medical Journal (2019)
18. Formononetin and Dihydroartemisinin Act Synergistically to Induce Apoptosis in Human Acute Myeloid Leukemia Cell Lines, Cell Journal (2024)
19. Blockage of Hotair Reduced Cell Proliferation in Human Ovarian Cancer Cells Through Upregulation of Akt2, Indian Journal of Gynecologic Oncology (2019)
20. Mechanism of Inositol-Requiring Enzyme 1-Alpha Inhibition in Endoplasmic Reticulum Stress and Apoptosis in Ovarian Cancer Cells, Journal of Cell Communication and Signaling (2020)
21. Her-2 Aptamer-Targeted Ecoflex® Nanoparticles Loaded With Docetaxel Promote Breast Cancer Cells Apoptosis and Anti-Metastatic Effect, IET Nanobiotechnology (2019)
22. Cytotoxic Effect of Drimia Maritima Bulb Extract and Induction of Mitochondrial Apoptotic Signaling in Human Breast Cancer Cells, Mcf-7 and Mda-Mb-468, OncoTargets and Therapy (2018)
23. Britannin, a Sesquiterpene Lactone, Inhibits Proliferation and Induces Apoptosis Through the Mitochondrial Signaling Pathway in Human Breast Cancer Cells, Tumor Biology (2015)
24. New 6(17)-Epoxylathyrane Diterpene: Aellinane From Euphorbia Aellenii Induces Apoptosis Via Mitochondrial Pathway in Ovarian Cancer Cell Line, Toxicology Mechanisms and Methods (2017)
25. All-Trans Retinoic Acid and Genistein Induce Cell Apoptosis in Ovcar-3 Cells by Increasing the P14 Tumor Suppressor Gene, Research in Pharmaceutical Sciences (2016)
26. Anticancer Activity of Delphinium Semibarbatum Alkaloid Fractions Against Lncap, and Du 145 Human Prostate Cancer Cells Through the Intrinsic Apoptotic Pathway, Iranian Journal of Pharmaceutical Research (2021)
27. Silibinin Exerts Anti-Cancer Activity on Human Ovarian Cancer Cells by Increasing Apoptosis and Inhibiting Epithelial-Mesenchymal Transition (Emt), Gene (2022)
28. Mitochondrial and Caspase Pathways Are Involved in the Induction of Apoptosis by Ib-Meca in Ovarian Cancer Cell Lines, Tumor Biology (2014)
29. Molecular Mechanisms of A3 Adenosine Receptor-Induced G1 Cell Cycle Arrest and Apoptosis in Androgen-Dependent and Independent Prostate Cancer Cell Lines: Involvement of Intrinsic Pathway, Journal of Cancer Research and Clinical Oncology (2011)
30. Molecular Mechanism of Apoptosis Induction by Gaillardin, a Sesquiterpene Lactone, in Breast Cancer Cell Lines: Gaillardin-Induced Apoptosis in Breast Cancer Cell Lines, Cell Biology and Toxicology (2015)
31. Centaurea Cyanus Extracted 13-O-Acetylsolstitialin a Decrease Bax/Bcl-2 Ratio and Expression of Cyclin D1/Cdk-4 to Induce Apoptosis and Cell Cycle Arrest in Mcf-7 and Mda-Mb-231 Breast Cancer Cell Lines, Journal of Cellular Biochemistry (2019)
32. The Effect of Adenosine A1 Receptor Agonist and Antagonist on P53 and Caspase 3, 8, and 9 Expression and Apoptosis Rate in Mcf-7 Breast Cancer Cell Line, Research in Pharmaceutical Sciences (2016)
33. Biodistribution, Safety and Organ Toxicity of Docetaxel-Loaded in Her-2 Aptamer Conjugated Ecoflex® Nanoparticles in a Mouse Xenograft Model of Ovarian Cancer, Recent Patents on Nanotechnology (2019)
34. Dihydroartemisinin Induces Apoptosis in Human Bladder Cancer Cell Lines Through Reactive Oxygen Species, Mitochondrial Membrane Potential, and Cytochrome C Pathway, International Journal of Preventive Medicine (2017)
35. Anti-Proliferative and Anti-Apoptotic Effects of Grape Seed Extract on Chemo-Resistant Ovcar-3 Ovarian Cancer Cells, Research in Pharmaceutical Sciences (2020)