30-hydroxygambogic acid increases the efficacy of cisplatin in an HPV+ head and neck cancer in vivo model
Abstract Background Head and neck squamous cell carcinoma (HNSCC) affects more than half a million people annually, and nearly 80% of oropharyngeal cancer cases are caused by human papillomavirus (HPV). Current treatments include chemo- and radiotherapy, though the effectiveness of these therapies i...
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BMC
2025-08-01
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| Online Access: | https://doi.org/10.1186/s12885-025-14638-3 |
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| author | Sonia N. Whang Valeria Rodarte Trevor Lohman Josh Barforough Lennox Chitsike Gina N. Lucas David Lee Caleb Ruiz-Jimenez Yan Chen Wongworawat Rouba Ali-Fehmi Marya Wahidi Juli Unternaehrer Valery Filippov Penelope J. Duerksen-Hughes |
| author_facet | Sonia N. Whang Valeria Rodarte Trevor Lohman Josh Barforough Lennox Chitsike Gina N. Lucas David Lee Caleb Ruiz-Jimenez Yan Chen Wongworawat Rouba Ali-Fehmi Marya Wahidi Juli Unternaehrer Valery Filippov Penelope J. Duerksen-Hughes |
| author_sort | Sonia N. Whang |
| collection | DOAJ |
| description | Abstract Background Head and neck squamous cell carcinoma (HNSCC) affects more than half a million people annually, and nearly 80% of oropharyngeal cancer cases are caused by human papillomavirus (HPV). Current treatments include chemo- and radiotherapy, though the effectiveness of these therapies is limited by the viral oncoprotein E6, which disrupts apoptotic pathways by binding and accelerating the degradation of molecules such as E6AP and caspase-8. Our lab has identified an E6 inhibitor, 30-hydroxygambogic acid (GA-OH), that is able to maintain these apoptotic signaling molecules. Method To further explore the therapeutic potential of this small molecule, we determined its antitumor efficacy in vivo. We developed an optimized xenograft model for HPV+ HNSCC, assessed GA-OH’s toxicity, and evaluated the effectiveness of GA-OH in combination with chemotherapy utilizing the optimized concentration of 0.6 mg/kg. Results GA-OH significantly increases (* p = 0.0105) cisplatin’s efficacy in HPV+ HNSCC in vivo without overt clinical manifestations. The only toxicities noted were a 4-fold increase in creatine kinase (**** p < 0.0001) and a 2.4-fold increase in aspartate aminotransferase (** p = 0.0057) in the cisplatin and GA-OH combination group compared to the vehicle group. Conclusion The small molecule GA-OH was tolerable in our murine model, significantly amplifying the efficacy of cisplatin treatment. |
| format | Article |
| id | doaj-art-9e02308a4f55486aa8a7f30f55b73ba3 |
| institution | DOAJ |
| issn | 1471-2407 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj-art-9e02308a4f55486aa8a7f30f55b73ba32025-08-20T03:05:09ZengBMCBMC Cancer1471-24072025-08-0125111510.1186/s12885-025-14638-330-hydroxygambogic acid increases the efficacy of cisplatin in an HPV+ head and neck cancer in vivo modelSonia N. Whang0Valeria Rodarte1Trevor Lohman2Josh Barforough3Lennox Chitsike4Gina N. Lucas5David Lee6Caleb Ruiz-Jimenez7Yan Chen Wongworawat8Rouba Ali-Fehmi9Marya Wahidi10Juli Unternaehrer11Valery Filippov12Penelope J. Duerksen-Hughes13Department of Basic Science, School of Medicine, Loma Linda UniversityDepartment of Basic Science, School of Medicine, Loma Linda UniversitySchool of Allied Health Professions, Loma Linda UniversityDepartment of Basic Science, School of Medicine, Loma Linda UniversityDepartment of Basic Science, School of Medicine, Loma Linda UniversityDepartment of Basic Science, School of Medicine, Loma Linda UniversityDepartment of Basic Science, School of Medicine, Loma Linda UniversityDepartment of Basic Science, School of Medicine, Loma Linda UniversityDepartment of Pathology and Human Anatomy, Loma Linda University Medical CenterDepartment of Pathology, Michigan Medicine, University of MichiganDepartment of Pathology, Michigan Medicine, University of MichiganDepartment of Basic Science, School of Medicine, Loma Linda UniversityDepartment of Basic Science, School of Medicine, Loma Linda UniversityDepartment of Basic Science, School of Medicine, Loma Linda UniversityAbstract Background Head and neck squamous cell carcinoma (HNSCC) affects more than half a million people annually, and nearly 80% of oropharyngeal cancer cases are caused by human papillomavirus (HPV). Current treatments include chemo- and radiotherapy, though the effectiveness of these therapies is limited by the viral oncoprotein E6, which disrupts apoptotic pathways by binding and accelerating the degradation of molecules such as E6AP and caspase-8. Our lab has identified an E6 inhibitor, 30-hydroxygambogic acid (GA-OH), that is able to maintain these apoptotic signaling molecules. Method To further explore the therapeutic potential of this small molecule, we determined its antitumor efficacy in vivo. We developed an optimized xenograft model for HPV+ HNSCC, assessed GA-OH’s toxicity, and evaluated the effectiveness of GA-OH in combination with chemotherapy utilizing the optimized concentration of 0.6 mg/kg. Results GA-OH significantly increases (* p = 0.0105) cisplatin’s efficacy in HPV+ HNSCC in vivo without overt clinical manifestations. The only toxicities noted were a 4-fold increase in creatine kinase (**** p < 0.0001) and a 2.4-fold increase in aspartate aminotransferase (** p = 0.0057) in the cisplatin and GA-OH combination group compared to the vehicle group. Conclusion The small molecule GA-OH was tolerable in our murine model, significantly amplifying the efficacy of cisplatin treatment.https://doi.org/10.1186/s12885-025-14638-3Human papillomavirus (HPV)Head and neck cancerHead and neck squamous cell carcinoma (HNSCC)30-hydroxygambogic acid (GA-OH)HPV+ mouse xenograftCombination therapy |
| spellingShingle | Sonia N. Whang Valeria Rodarte Trevor Lohman Josh Barforough Lennox Chitsike Gina N. Lucas David Lee Caleb Ruiz-Jimenez Yan Chen Wongworawat Rouba Ali-Fehmi Marya Wahidi Juli Unternaehrer Valery Filippov Penelope J. Duerksen-Hughes 30-hydroxygambogic acid increases the efficacy of cisplatin in an HPV+ head and neck cancer in vivo model BMC Cancer Human papillomavirus (HPV) Head and neck cancer Head and neck squamous cell carcinoma (HNSCC) 30-hydroxygambogic acid (GA-OH) HPV+ mouse xenograft Combination therapy |
| title | 30-hydroxygambogic acid increases the efficacy of cisplatin in an HPV+ head and neck cancer in vivo model |
| title_full | 30-hydroxygambogic acid increases the efficacy of cisplatin in an HPV+ head and neck cancer in vivo model |
| title_fullStr | 30-hydroxygambogic acid increases the efficacy of cisplatin in an HPV+ head and neck cancer in vivo model |
| title_full_unstemmed | 30-hydroxygambogic acid increases the efficacy of cisplatin in an HPV+ head and neck cancer in vivo model |
| title_short | 30-hydroxygambogic acid increases the efficacy of cisplatin in an HPV+ head and neck cancer in vivo model |
| title_sort | 30 hydroxygambogic acid increases the efficacy of cisplatin in an hpv head and neck cancer in vivo model |
| topic | Human papillomavirus (HPV) Head and neck cancer Head and neck squamous cell carcinoma (HNSCC) 30-hydroxygambogic acid (GA-OH) HPV+ mouse xenograft Combination therapy |
| url | https://doi.org/10.1186/s12885-025-14638-3 |
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