Next Article in Journal
Retinoids Delivery Systems in Cancer: Liposomal Fenretinide for Neuroectodermal-Derived Tumors
Next Article in Special Issue
Endothelial Thioredoxin-Interacting Protein Depletion Reduces Hemorrhagic Transformation in Hyperglycemic Mice after Embolic Stroke and Thrombolytic Therapy
Previous Article in Journal
Improved HDAC Inhibition, Stronger Cytotoxic Effect and Higher Selectivity against Leukemias and Lymphomas of Novel, Tricyclic Vorinostat Analogues
Previous Article in Special Issue
Protective Effect of Piplartine against LPS-Induced Sepsis through Attenuating the MAPKs/NF-κB Signaling Pathway and NLRP3 Inflammasome Activation
Article

Doxycycline Attenuates Cancer Cell Growth by Suppressing NLRP3-Mediated Inflammation

1
Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia
2
Department of Fundamental Sciences, Faculty of Dentistry, Bursa Uludag University, Bursa 16059, Turkey
3
Centre for Cancer Sciences, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham NG7 2RD, UK
4
Department of Microbiology and Immunology, University of Nevada, Reno, NV 89557, USA
*
Authors to whom correspondence should be addressed.
Academic Editors: Concetta Saponaro, Raffaella Soleti, Simona De Summa and Antonia Cianciulli
Pharmaceuticals 2021, 14(9), 852; https://0-doi-org.brum.beds.ac.uk/10.3390/ph14090852
Received: 28 July 2021 / Revised: 23 August 2021 / Accepted: 24 August 2021 / Published: 26 August 2021
NLR family pyrin domain containing 3 (NLRP3) inflammasome formation is triggered by the damaged mitochondria releasing reactive oxygen species. Doxycycline was shown to regulate inflammation; however, its effect on NLRP3 in cancer remains largely unknown. Therefore, we sought to determine the effect of doxycycline on NLRP3 regulation in cancer using an in vitro model. NLRP3 was activated in a prostate cancer cell line (PC3) and a lung cancer cell line (A549) before treatment with doxycycline. Inflammasome activation was assessed by analyzing RNA expression of NLRP3, Pro-CASP-1, and Pro-IL1β using RT-qPCR. Additionally, NLPR3 protein expression and IL-1β secretion were analyzed using Western blot and ELISA, respectively. Tumor cell viability was determined using Annexin V staining and a cell proliferation assay. Cytokine secretion was analyzed using a 41Plex assay for human cytokines. Data were analyzed using one-way ANOVA model with Tukey’s post hoc tests. Doxycycline treatment decreased NLRP3 formation in PC3 and A549 cells compared to untreated and LPS only treated cells (p < 0.05). Doxycycline also decreased proliferation and caused cell death through apoptosis, a response that differed to the LPS-Nigericin mediated pyroptosis. Our findings suggest that doxycycline inhibits LPS priming of NLRP3 and reduces tumor progression through early apoptosis in cancer. View Full-Text
Keywords: doxycycline; nod-like receptor protein 3 (NLRP3); inflammasome; apoptosis; cancer doxycycline; nod-like receptor protein 3 (NLRP3); inflammasome; apoptosis; cancer
Show Figures

Graphical abstract

MDPI and ACS Style

Alsaadi, M.; Tezcan, G.; Garanina, E.E.; Hamza, S.; McIntyre, A.; Rizvanov, A.A.; Khaiboullina, S.F. Doxycycline Attenuates Cancer Cell Growth by Suppressing NLRP3-Mediated Inflammation. Pharmaceuticals 2021, 14, 852. https://0-doi-org.brum.beds.ac.uk/10.3390/ph14090852

AMA Style

Alsaadi M, Tezcan G, Garanina EE, Hamza S, McIntyre A, Rizvanov AA, Khaiboullina SF. Doxycycline Attenuates Cancer Cell Growth by Suppressing NLRP3-Mediated Inflammation. Pharmaceuticals. 2021; 14(9):852. https://0-doi-org.brum.beds.ac.uk/10.3390/ph14090852

Chicago/Turabian Style

Alsaadi, Mohammad, Gulcin Tezcan, Ekaterina E. Garanina, Shaimaa Hamza, Alan McIntyre, Albert A. Rizvanov, and Svetlana F. Khaiboullina. 2021. "Doxycycline Attenuates Cancer Cell Growth by Suppressing NLRP3-Mediated Inflammation" Pharmaceuticals 14, no. 9: 852. https://0-doi-org.brum.beds.ac.uk/10.3390/ph14090852

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop