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Serotonin's Role in Inflammatory Signaling Pathway Modulation for Colon Cancer Suppression
Supreeta Maheshwarla Saravanan1, Lavanya Prathap1, Jabir Padathpeedika Khalid2
1Department of Anatomy, Biomedical Research Unit and Laboratory Animal Centre (BRULAC) Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, IND.
Abstract:
Background Neurons can be effectively regulated by serotonin and dopamine. Their role in anti-inflammatory pathways opens new doors for therapeutic research, particularly in chemotherapeutics. The present study investigated serotonin's role in suppressing inflammation and its potential anticancer effects in KERATIN-forming tumor cell line HeLa cells (KB cells). Methods - in vitro and in silico analysis The study delved further into the molecular mechanisms by assessing the expression levels of key markers involved in inflammation and cancer progression, such as B-cell leukemia/lymphoma 2 protein (BCl-2), tumor necrosis factor-alpha (TNF-α) and Interleukin-6 (IL-6) using Real-time reverse-transcriptase-polymerase chain reaction at concentrations below the IC50 (50 and 100 µg/ml). The binding capability of serotonin (CID 5202) with glycoform of human interleukin 6 (PDB: 7NXZ) was analyzed with the help of Schrodinger molecular suites. Results The findings showcased serotonin's potent growth inhibition in KB cells, with an IC50 value of 225±3.1µg/ml. Additionally, it demonstrated a multifaceted impact by downregulating the expression of BCl-2, TNF-α, and IL-6, pivotal factors in cancer cell survival and inflammation regulation. The docking score was - 5.65 (kcal/mol) between serotonin and glycoform of Human Interleukin 6. It is bound with ASN 143 by two hydrogen bonds. Thus, molecular docking analysis showed an efficient bounding pattern. The research findings indicate that serotonin successfully blocks NF-κB pathways in KB cells, underscoring its therapeutic promise against colon cancer and offering vital information for additional clinical investigation. Conclusion According to the study's conclusion, serotonin has a remarkable anticancer potential by effectively blocking NF-κB B pathways in KB cells, revealing its promising potential as a therapeutic agent against colon cancer. These comprehensive findings offer significant insights into serotonin's intricate molecular interactions and its profound impact on cancer-related signaling pathways, paving the way for further exploration and potential clinical applications in cancer treatment strategies.
Insights
Serotonin effectively inhibits growth and downregulates key inflammatory and cancer markers in KB cells. This study highlights serotonin
Area of Science:
- Oncology
- Neuroscience
- Molecular Biology
Background:
- Serotonin and dopamine regulate neurons, with potential in anti-inflammatory and chemotherapeutic research.
- The study focuses on serotonin's anti-inflammatory and anticancer effects in HeLa (KB) cells.
Purpose of the Study:
- Investigate serotonin's role in suppressing inflammation and its anticancer potential in KB cells.
- Analyze molecular mechanisms of serotonin's action, including its interaction with Interleukin-6.
Main Methods:
- In vitro and in silico analysis of serotonin's effects on KB cells.
- Real-time RT-PCR to assess B-cell leukemia/lymphoma 2 protein (BCl-2), tumor necrosis factor-alpha (TNF-α), and Interleukin-6 (IL-6) expression.
- Molecular docking using Schrodinger suites to analyze serotonin binding with human Interleukin-6.
Main Results:
- Serotonin demonstrated significant growth inhibition in KB cells (IC50: 225±3.1µg/ml).
- Downregulation of BCl-2, TNF-α, and IL-6 expression observed.
- Molecular docking revealed efficient binding of serotonin to human Interleukin-6 (docking score: -5.65 kcal/mol).
- Serotonin blocked NF-κB pathways in KB cells.
Conclusions:
- Serotonin exhibits significant anticancer potential by blocking NF-κB pathways in KB cells.
- Findings suggest serotonin as a promising therapeutic agent for colon cancer.
- The study provides insights into serotonin's molecular interactions for potential clinical applications.
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