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Protective Effect of Piplartine against LPS-Induced Sepsis through Attenuating the MAPKs/NF-κB Signaling Pathway and NLRP3 Inflammasome Activation

Doxycycline Attenuates Cancer Cell Growth by Suppressing NLRP3-Mediated Inflammation

Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia
Department of Fundamental Sciences, Faculty of Dentistry, Bursa Uludag University, Bursa 16059, Turkey
Centre for Cancer Sciences, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham NG7 2RD, UK
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;
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
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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.

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.

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.

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