Friedelin induces apoptosis in oral cancer: Insights from in vitro and in silico studies

Background: Oral cancer is a major health issue in the world because of its high morbidity and mortality rates. Dysregulated apoptosis, is involved in tumor progression and treatment resistance. Friedelin, a natural triterpenoid, has been shown to have potential to modulate apoptosis pathways. This...

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Main Authors: Ramya Sekar, Monisha Prasad, Manikandan Alagumuthu
Format: Article
Language:English
Published: Elsevier 2025-11-01
Series:Journal of Oral Biology and Craniofacial Research
Online Access:http://www.sciencedirect.com/science/article/pii/S2212426825001927
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author Ramya Sekar
Monisha Prasad
Manikandan Alagumuthu
author_facet Ramya Sekar
Monisha Prasad
Manikandan Alagumuthu
author_sort Ramya Sekar
collection DOAJ
description Background: Oral cancer is a major health issue in the world because of its high morbidity and mortality rates. Dysregulated apoptosis, is involved in tumor progression and treatment resistance. Friedelin, a natural triterpenoid, has been shown to have potential to modulate apoptosis pathways. This study investigates the therapeutic effects of Friedelin, particularly on its interactions with apoptotic proteins, cytotoxic effects on KB oral cancer cells, and ability to induce apoptosis through intrinsic signaling pathways. Materials and methods: Interaction networks were constructed by taking target genes related to Friedelin and oral cancer identified by CTD and GeneCards, and applying them in the STITCH database for analysis. Apoptotic binding affinity of key proteins, towards Friedelin was determined using molecular docking. The cytotoxic potential of Friedelin was accessed by performing in vitro assays such as MTT, morphology analysis, and Annexin V-FITC flow cytometry. The regulation of Friedelin on apoptosis was validated through gene expression analysis. Results: Network analysis identified Friedelin's critical interactions with apoptotic regulators. Molecular docking revealed strong binding affinities, particularly with Bax (−8.3 kcal/mol) and Bcl2 (−8.0 kcal/mol). Cytotoxicity assays showed dose- and time-dependent effects. Gene expression analysis confirmed upregulation of Bax, Caspase-3, and TP53, and downregulation of Bcl2, demonstrating activation of intrinsic apoptotic pathways. Conclusion: Friedelin is an anticancer agent that has great potential for oral cancer treatment by modulating apoptotic signaling pathways and inducing apoptosis. Future studies should be conducted on the in vivo validation and clinical translation of Friedelin as a novel therapeutic candidate.
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spelling doaj-art-7d620cc059cf487caad4438e7c33b98d2025-08-22T04:56:16ZengElsevierJournal of Oral Biology and Craniofacial Research2212-42682025-11-011561354136010.1016/j.jobcr.2025.08.013Friedelin induces apoptosis in oral cancer: Insights from in vitro and in silico studiesRamya Sekar0Monisha Prasad1Manikandan Alagumuthu2Department of Oral & Maxillofacial Pathology and Oral Microbiology, Meenakshi Ammal Dental College and Hospital, Meenakshi Academy of Higher Education and Research (Deemed to be University), Chennai, Tamil Nadu, IndiaMolecular Nutrition and Genomics Lab, Department of Community Medicine, Saveetha Medical College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, 602105, India; Corresponding author: Molecular Nutrition and Genomics Lab, Department of Community Medicine, Saveetha Medical College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, 602105, IndiaDepartment of Microbiology, Saveetha Medical College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, 602105, IndiaBackground: Oral cancer is a major health issue in the world because of its high morbidity and mortality rates. Dysregulated apoptosis, is involved in tumor progression and treatment resistance. Friedelin, a natural triterpenoid, has been shown to have potential to modulate apoptosis pathways. This study investigates the therapeutic effects of Friedelin, particularly on its interactions with apoptotic proteins, cytotoxic effects on KB oral cancer cells, and ability to induce apoptosis through intrinsic signaling pathways. Materials and methods: Interaction networks were constructed by taking target genes related to Friedelin and oral cancer identified by CTD and GeneCards, and applying them in the STITCH database for analysis. Apoptotic binding affinity of key proteins, towards Friedelin was determined using molecular docking. The cytotoxic potential of Friedelin was accessed by performing in vitro assays such as MTT, morphology analysis, and Annexin V-FITC flow cytometry. The regulation of Friedelin on apoptosis was validated through gene expression analysis. Results: Network analysis identified Friedelin's critical interactions with apoptotic regulators. Molecular docking revealed strong binding affinities, particularly with Bax (−8.3 kcal/mol) and Bcl2 (−8.0 kcal/mol). Cytotoxicity assays showed dose- and time-dependent effects. Gene expression analysis confirmed upregulation of Bax, Caspase-3, and TP53, and downregulation of Bcl2, demonstrating activation of intrinsic apoptotic pathways. Conclusion: Friedelin is an anticancer agent that has great potential for oral cancer treatment by modulating apoptotic signaling pathways and inducing apoptosis. Future studies should be conducted on the in vivo validation and clinical translation of Friedelin as a novel therapeutic candidate.http://www.sciencedirect.com/science/article/pii/S2212426825001927
spellingShingle Ramya Sekar
Monisha Prasad
Manikandan Alagumuthu
Friedelin induces apoptosis in oral cancer: Insights from in vitro and in silico studies
Journal of Oral Biology and Craniofacial Research
title Friedelin induces apoptosis in oral cancer: Insights from in vitro and in silico studies
title_full Friedelin induces apoptosis in oral cancer: Insights from in vitro and in silico studies
title_fullStr Friedelin induces apoptosis in oral cancer: Insights from in vitro and in silico studies
title_full_unstemmed Friedelin induces apoptosis in oral cancer: Insights from in vitro and in silico studies
title_short Friedelin induces apoptosis in oral cancer: Insights from in vitro and in silico studies
title_sort friedelin induces apoptosis in oral cancer insights from in vitro and in silico studies
url http://www.sciencedirect.com/science/article/pii/S2212426825001927
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AT monishaprasad friedelininducesapoptosisinoralcancerinsightsfrominvitroandinsilicostudies
AT manikandanalagumuthu friedelininducesapoptosisinoralcancerinsightsfrominvitroandinsilicostudies