Inhibition of Retinoblastoma Cell Growth by Boswellic Acid Through Activation of the Suppressing Nuclear Factor—κB Activation

<i>Background and Objectives:</i> Despite the development of treatment methods and the emergence of alternative new approaches in recent years, the visual prognosis of retinoblastoma contains deficiencies and this situation increases the need for the development of new treatment approach...

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Main Authors: Semih Doğan, Mehmet Cudi Tuncer, İlhan Özdemir
Format: Article
Language:English
Published: MDPI AG 2025-03-01
Series:Medicina
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Online Access:https://www.mdpi.com/1648-9144/61/3/480
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author Semih Doğan
Mehmet Cudi Tuncer
İlhan Özdemir
author_facet Semih Doğan
Mehmet Cudi Tuncer
İlhan Özdemir
author_sort Semih Doğan
collection DOAJ
description <i>Background and Objectives:</i> Despite the development of treatment methods and the emergence of alternative new approaches in recent years, the visual prognosis of retinoblastoma contains deficiencies and this situation increases the need for the development of new treatment approaches. The cytotoxic and apoptosis-inducing effects of the combination of boswellic acid (BA), which has been determined to have significant potential in preclinical and clinical studies of various diseases, and Cisplatin (Cis), a potent chemotherapy agent, were investigated on the human retinoblastoma cell line (Y79). <i>Materials and Methods:</i> The cytotoxic effect of BA and Cis on Y79 cells was determined by the water soluble tetrazolium-1 (WST-1) test, the apoptotic rate of the cells was determined by annexin V staining, and the gene expressions of <i>Protein53 (p53)</i>, <i>Caspase-3</i> and <i>Nuclear factor kappa B (NF-κB)</i>, which play an important role in apoptosis, were determined by RT-qPCR analysis. Interleukin 1-beta (IL1-β), tumor necrosis factor-α (TNF-α) and interferon γ (IFN-γ) levels were analyzed in cell lysates obtained from the experimental groups. <i>Results:</i> The combination of BA and Cis selectively inhibited the growth of Y79 cells and modulated <i>NF-κB</i> signaling, potentially through post-translational regulatory mechanisms. Moreover, it induced apoptosis by increasing <i>p53</i> and <i>Caspase-3</i> expressions, confirming its pro-apoptotic effects. Additionally, the combination treatment was associated with a reduction in inflammatory cytokine levels (TNF-α, IL1-β), suggesting a potential regulatory effect on inflammation-related pathways rather than direct inhibition of <i>NF-κB</i> activation. <i>Conclusions:</i> These findings suggest that BA combined with Cis inhibits Y79 retinoblastoma cell growth by inducing apoptosis and modulating <i>NF-κB</i> signaling. While <i>NF-κB</i> mRNA levels increased, reduced inflammatory cytokines and enhanced apoptosis suggest potential post-translational regulation. Further studies are needed to confirm <i>NF-κB</i> protein-level effects and in vivo efficacy.
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spelling doaj-art-aefeabfabcb24ac9b2d11b20997a36b72025-08-20T02:11:04ZengMDPI AGMedicina1010-660X1648-91442025-03-0161348010.3390/medicina61030480Inhibition of Retinoblastoma Cell Growth by Boswellic Acid Through Activation of the Suppressing Nuclear Factor—κB ActivationSemih Doğan0Mehmet Cudi Tuncer1İlhan Özdemir2Department of Ophthalmology, Faculty of Medicine, Beykent University, İstanbul 34398, TurkeyDepartment of Anatomy, Faculty of Medicine, Dicle University, Diyarbakır 21280, TurkeyDepartment of Gynecology and Obstetrics, Faculty of Medicine, Atatürk University, Erzurum 25240, Turkey<i>Background and Objectives:</i> Despite the development of treatment methods and the emergence of alternative new approaches in recent years, the visual prognosis of retinoblastoma contains deficiencies and this situation increases the need for the development of new treatment approaches. The cytotoxic and apoptosis-inducing effects of the combination of boswellic acid (BA), which has been determined to have significant potential in preclinical and clinical studies of various diseases, and Cisplatin (Cis), a potent chemotherapy agent, were investigated on the human retinoblastoma cell line (Y79). <i>Materials and Methods:</i> The cytotoxic effect of BA and Cis on Y79 cells was determined by the water soluble tetrazolium-1 (WST-1) test, the apoptotic rate of the cells was determined by annexin V staining, and the gene expressions of <i>Protein53 (p53)</i>, <i>Caspase-3</i> and <i>Nuclear factor kappa B (NF-κB)</i>, which play an important role in apoptosis, were determined by RT-qPCR analysis. Interleukin 1-beta (IL1-β), tumor necrosis factor-α (TNF-α) and interferon γ (IFN-γ) levels were analyzed in cell lysates obtained from the experimental groups. <i>Results:</i> The combination of BA and Cis selectively inhibited the growth of Y79 cells and modulated <i>NF-κB</i> signaling, potentially through post-translational regulatory mechanisms. Moreover, it induced apoptosis by increasing <i>p53</i> and <i>Caspase-3</i> expressions, confirming its pro-apoptotic effects. Additionally, the combination treatment was associated with a reduction in inflammatory cytokine levels (TNF-α, IL1-β), suggesting a potential regulatory effect on inflammation-related pathways rather than direct inhibition of <i>NF-κB</i> activation. <i>Conclusions:</i> These findings suggest that BA combined with Cis inhibits Y79 retinoblastoma cell growth by inducing apoptosis and modulating <i>NF-κB</i> signaling. While <i>NF-κB</i> mRNA levels increased, reduced inflammatory cytokines and enhanced apoptosis suggest potential post-translational regulation. Further studies are needed to confirm <i>NF-κB</i> protein-level effects and in vivo efficacy.https://www.mdpi.com/1648-9144/61/3/480retinoblastoma<i>NF-κB</i> geneboswellic acidoxidative stress
spellingShingle Semih Doğan
Mehmet Cudi Tuncer
İlhan Özdemir
Inhibition of Retinoblastoma Cell Growth by Boswellic Acid Through Activation of the Suppressing Nuclear Factor—κB Activation
Medicina
retinoblastoma
<i>NF-κB</i> gene
boswellic acid
oxidative stress
title Inhibition of Retinoblastoma Cell Growth by Boswellic Acid Through Activation of the Suppressing Nuclear Factor—κB Activation
title_full Inhibition of Retinoblastoma Cell Growth by Boswellic Acid Through Activation of the Suppressing Nuclear Factor—κB Activation
title_fullStr Inhibition of Retinoblastoma Cell Growth by Boswellic Acid Through Activation of the Suppressing Nuclear Factor—κB Activation
title_full_unstemmed Inhibition of Retinoblastoma Cell Growth by Boswellic Acid Through Activation of the Suppressing Nuclear Factor—κB Activation
title_short Inhibition of Retinoblastoma Cell Growth by Boswellic Acid Through Activation of the Suppressing Nuclear Factor—κB Activation
title_sort inhibition of retinoblastoma cell growth by boswellic acid through activation of the suppressing nuclear factor κb activation
topic retinoblastoma
<i>NF-κB</i> gene
boswellic acid
oxidative stress
url https://www.mdpi.com/1648-9144/61/3/480
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AT ilhanozdemir inhibitionofretinoblastomacellgrowthbyboswellicacidthroughactivationofthesuppressingnuclearfactorkbactivation