Sodium Butyrate: A Multifaceted Modulator in Colorectal Cancer Therapy
<i>Background and Objectives</i>: Sodium butyrate (NaB) is a potent modulator of cancer-related gene networks. However, its precise mechanisms of action and effects at elevated doses remain insufficiently explored. This study investigated the impact of NaB at physiologically relevant dos...
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2025-01-01
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| author | Alexandra Laura Mederle Alexandra Semenescu George Andrei Drăghici Cristina Adriana Dehelean Nicolae-Valentin Vlăduț Dragoş Vasile Nica |
| author_facet | Alexandra Laura Mederle Alexandra Semenescu George Andrei Drăghici Cristina Adriana Dehelean Nicolae-Valentin Vlăduț Dragoş Vasile Nica |
| author_sort | Alexandra Laura Mederle |
| collection | DOAJ |
| description | <i>Background and Objectives</i>: Sodium butyrate (NaB) is a potent modulator of cancer-related gene networks. However, its precise mechanisms of action and effects at elevated doses remain insufficiently explored. This study investigated the impact of NaB at physiologically relevant doses on key cellular metrics (viability, confluence, cell number, morphology, nuclear integrity) and a comprehensive set of apoptosis and proliferation regulators (including underexplored genes) in colorectal cancer (CRC) cells. <i>Materials and Methods</i>: Human HCT-116 cells were treated with increasing NaB concentrations (0–20 mM). Cell viability, confluence, number, morphology, and nuclear integrity were assessed using MTT and imaging assays. RT-PCR was used to determine changes in the expression of critical pro-apoptotic players (<i>BAX</i>, <i>CASP3</i>, <i>PUMA</i>, <i>TP53</i>), anti-apoptotic facilitators (<i>BCL</i>-2, <i>MCL-1</i>), cell division regulators (<i>PCNA</i>, <i>Ki-67</i>, <i>CDKN</i>1), and inflammation genes (<i>NF-κB</i>). <i>Results:</i> This study provides the first exploration of <i>MCL-1</i> and <i>PCNA</i> modulation by NaB in the context of CRC and HCT-116 cells, offering significant translational insights. All treatments reduced cell viability, confluence, and number in a dose-dependent manner (<i>p</i> < 0.0001). Gene expression revealed dose-related increases in most pro-apoptotic markers (<i>BAX</i>, <i>CASP3</i>, <i>PUMA</i>; <i>p</i> < 0.001), and decreases for the other genes (<i>p</i> < 0.001). BAX emerged as the most responsive gene to NaB, while TP53 showed minimal sensitivity, supporting NaB’s effectiveness in p53-compromised phenotypes. Nuclear condensation and fragmentation at higher NaB doses confirmed apoptotic induction. <i>Conclusions</i>: NaB can modulate critical apoptotic and cell cycle genes, disrupt tumor cell proliferation, and overcome resistance mechanisms associated with anti-apoptotic regulators such as <i>MCL-1</i>. By targeting both short-term and long-term anti-apoptotic defenses, NaB shows promise as a preventive and therapeutic agent in CRC, particularly in high-risk phenotypes with compromised p53 functionality. These findings support its potential for integration into combination therapies or dietary interventions aimed at enhancing colonic butyrate levels. |
| format | Article |
| id | doaj-art-49064be5c5774809a692391c7b26f364 |
| institution | Kabale University |
| issn | 1010-660X 1648-9144 |
| language | English |
| publishDate | 2025-01-01 |
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| spelling | doaj-art-49064be5c5774809a692391c7b26f3642025-01-24T13:40:47ZengMDPI AGMedicina1010-660X1648-91442025-01-0161113610.3390/medicina61010136Sodium Butyrate: A Multifaceted Modulator in Colorectal Cancer TherapyAlexandra Laura Mederle0Alexandra Semenescu1George Andrei Drăghici2Cristina Adriana Dehelean3Nicolae-Valentin Vlăduț4Dragoş Vasile Nica5Doctoral School, “Victor Babeș” University of Medicine and Pharmacy Timişoara, Eftimie Murgu Square No. 2, 300041 Timișoara, RomaniaFaculty of Pharmacy, “Victor Babeș” University of Medicine and Pharmacy Timișoara, Eftimie Murgu Square No. 2, 300041 Timișoara, RomaniaFaculty of Pharmacy, “Victor Babeș” University of Medicine and Pharmacy Timișoara, Eftimie Murgu Square No. 2, 300041 Timișoara, RomaniaFaculty of Pharmacy, “Victor Babeș” University of Medicine and Pharmacy Timișoara, Eftimie Murgu Square No. 2, 300041 Timișoara, RomaniaThe National Institute of Research—Development for Machines and Installations Designed for Agriculture and Food Industry (INMA), Bulevardul Ion Ionescu de la Brad 6, 077190 București, RomaniaResearch Center for Pharmaco-Toxicological Evaluations, Faculty of Pharmacy,“Victor Babeş” University of Medicine and Pharmacy Timișoara, Eftimie Murgu Square No. 2, 300041 Timișoara, Romania<i>Background and Objectives</i>: Sodium butyrate (NaB) is a potent modulator of cancer-related gene networks. However, its precise mechanisms of action and effects at elevated doses remain insufficiently explored. This study investigated the impact of NaB at physiologically relevant doses on key cellular metrics (viability, confluence, cell number, morphology, nuclear integrity) and a comprehensive set of apoptosis and proliferation regulators (including underexplored genes) in colorectal cancer (CRC) cells. <i>Materials and Methods</i>: Human HCT-116 cells were treated with increasing NaB concentrations (0–20 mM). Cell viability, confluence, number, morphology, and nuclear integrity were assessed using MTT and imaging assays. RT-PCR was used to determine changes in the expression of critical pro-apoptotic players (<i>BAX</i>, <i>CASP3</i>, <i>PUMA</i>, <i>TP53</i>), anti-apoptotic facilitators (<i>BCL</i>-2, <i>MCL-1</i>), cell division regulators (<i>PCNA</i>, <i>Ki-67</i>, <i>CDKN</i>1), and inflammation genes (<i>NF-κB</i>). <i>Results:</i> This study provides the first exploration of <i>MCL-1</i> and <i>PCNA</i> modulation by NaB in the context of CRC and HCT-116 cells, offering significant translational insights. All treatments reduced cell viability, confluence, and number in a dose-dependent manner (<i>p</i> < 0.0001). Gene expression revealed dose-related increases in most pro-apoptotic markers (<i>BAX</i>, <i>CASP3</i>, <i>PUMA</i>; <i>p</i> < 0.001), and decreases for the other genes (<i>p</i> < 0.001). BAX emerged as the most responsive gene to NaB, while TP53 showed minimal sensitivity, supporting NaB’s effectiveness in p53-compromised phenotypes. Nuclear condensation and fragmentation at higher NaB doses confirmed apoptotic induction. <i>Conclusions</i>: NaB can modulate critical apoptotic and cell cycle genes, disrupt tumor cell proliferation, and overcome resistance mechanisms associated with anti-apoptotic regulators such as <i>MCL-1</i>. By targeting both short-term and long-term anti-apoptotic defenses, NaB shows promise as a preventive and therapeutic agent in CRC, particularly in high-risk phenotypes with compromised p53 functionality. These findings support its potential for integration into combination therapies or dietary interventions aimed at enhancing colonic butyrate levels.https://www.mdpi.com/1648-9144/61/1/136sodium butyratecolorectal cancerCRCapoptosis |
| spellingShingle | Alexandra Laura Mederle Alexandra Semenescu George Andrei Drăghici Cristina Adriana Dehelean Nicolae-Valentin Vlăduț Dragoş Vasile Nica Sodium Butyrate: A Multifaceted Modulator in Colorectal Cancer Therapy Medicina sodium butyrate colorectal cancer CRC apoptosis |
| title | Sodium Butyrate: A Multifaceted Modulator in Colorectal Cancer Therapy |
| title_full | Sodium Butyrate: A Multifaceted Modulator in Colorectal Cancer Therapy |
| title_fullStr | Sodium Butyrate: A Multifaceted Modulator in Colorectal Cancer Therapy |
| title_full_unstemmed | Sodium Butyrate: A Multifaceted Modulator in Colorectal Cancer Therapy |
| title_short | Sodium Butyrate: A Multifaceted Modulator in Colorectal Cancer Therapy |
| title_sort | sodium butyrate a multifaceted modulator in colorectal cancer therapy |
| topic | sodium butyrate colorectal cancer CRC apoptosis |
| url | https://www.mdpi.com/1648-9144/61/1/136 |
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