Exploring the Therapeutic Potential of Triptonide in Salivary Adenoid Cystic Carcinoma: A Comprehensive Approach Involving Network Pharmacology and Experimental Validation

Title:Exploring the Therapeutic Potential of Triptonide in Salivary Adenoid Cystic Carcinoma: A Comprehensive Approach Involving Network Pharmacology and Experimental Validation

Volume: 30 Issue: 29

Author(s): Shikai Geng, Li Chen, Wanzun Lin, Fangzhu Wan, Ziyu Le, Wei Hu, Huaiyuan Chen, Xingyu Liu, Qingting Huang, Haojiong Zhang, Jiade J. Lu and Lin Kong*

Affiliation:

• Department of Radiation Oncology, Shanghai Proton and Heavy Ion Center, Fudan University Shanghai Cancer Center, Shanghai, China
• Shanghai Key Laboratory of Radiation Oncology (20dz2261000), Shanghai Engineering Research Center of Proton and Heavy Ion Radiation Therapy, Shanghai, China
• Department of Radiation Oncology, Shanghai Proton and Heavy Ion Center, Shanghai, China

Abstract:

Background: Salivary Adenoid Cystic Carcinoma (ACC) is characterized by a highly invasive and slow-growing pattern, and its etiology remains unidentified. Triptonide (TN) has demonstrated efficacy as a pharmacotherapeutic agent against ACC. Nonetheless, the specific targets and mechanism of molecular action underlying the effectiveness of TN in treating ACC have not been elucidated.

Objectives: By integrating network pharmacology within laboratory experiments, this research delves into the prospective targets and molecular mechanisms associated with the application of TN in treating ACC.

Methods: Initially, pertinent targets associated with TN against ACC were acquired from public databases. Subsequently, a combination of network pharmacology and bioinformatics analysis was utilized to screen the top 10 hub targets and key signal pathways of TN-treating ACC. Finally, in vitro experiments involving various molecular assays were conducted to evaluate the biological phenotypes of cells following TN treatment, encompassing assessments of apoptosis levels, plate migration, and other parameters, thereby validating pivotal genes and pathways.

Results: A total of 23 pertinent targets for TN in relation to ACC were identified, with the top 10 hub genes being MAPK8, PTGS2, RELA, MAPK14, NR3C1, HDAC1, PPARG, NFKBIA, AR, and PGR. There was a significant correlation between the TNF signaling pathway and the treatment of ACC with TN. In vitro experiments demonstrated that TN treatment elevated RELA phosphorylation while concurrently reducing MAPK14 phosphorylation and inducing G2/M arrest. TN exhibited the ability to enhance the apoptosis rate through increased caspase-3 activity, elevated levels of Reactive Oxygen Species (ROS), mitochondrial dysfunction, and inhibition of cell migration.

Conclusion: There is a potential therapeutic role for TN in the treatment of ACC through the activation of the TNF signaling pathway. Among the identified candidates, MAPK8, HDAC1, PTGS2, RELA, NR3C1, PPARG, NFKBIA, AR, and PGR emerge as the most pertinent therapeutic targets for TN in the context of ACC treatment.

Cite this article as:

Geng Shikai, Chen Li, Lin Wanzun, Wan Fangzhu, Le Ziyu, Hu Wei, Chen Huaiyuan, Liu Xingyu, Huang Qingting, Zhang Haojiong, Lu J. Jiade and Kong Lin*, Exploring the Therapeutic Potential of Triptonide in Salivary Adenoid Cystic Carcinoma: A Comprehensive Approach Involving Network Pharmacology and Experimental Validation, Current Pharmaceutical Design 2024; 30 (29) . https://dx.doi.org/10.2174/0113816128315277240610052453