Synergistic anticancer effects of cisplatin and phenolic aglycones of the aerial part of Rumex dentatus L. in tongue squamous cell carcinoma: insights from network pharmacology and biological verification

Abstract Background Oral squamous cell carcinoma (OSCC) ranks as the sixth most common malignancy globally. Cisplatin is the standard chemotherapy for OSCC, but resistance often reduces its efficacy, necessitating new treatments with fewer side effects. Rumex dentatus L., from the Polygonaceae famil...

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Main Authors: Amany E. Ragab, Ghada M. Al-Ashmawy, Sherin R. El Afify, Ola A. El-Feky, Amera O. Ibrahim
Format: Article
Language:English
Published: BMC 2025-01-01
Series:BMC Complementary Medicine and Therapies
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Online Access:https://doi.org/10.1186/s12906-024-04718-5
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author Amany E. Ragab
Ghada M. Al-Ashmawy
Sherin R. El Afify
Ola A. El-Feky
Amera O. Ibrahim
author_facet Amany E. Ragab
Ghada M. Al-Ashmawy
Sherin R. El Afify
Ola A. El-Feky
Amera O. Ibrahim
author_sort Amany E. Ragab
collection DOAJ
description Abstract Background Oral squamous cell carcinoma (OSCC) ranks as the sixth most common malignancy globally. Cisplatin is the standard chemotherapy for OSCC, but resistance often reduces its efficacy, necessitating new treatments with fewer side effects. Rumex dentatus L., from the Polygonaceae family, is known for its medicinal properties, but its anticancer potential has not been thoroughly explored. This study aimed to investigate the synergy between cisplatin and an extract from the aerial parts of R. dentatus L. in treating tongue carcinoma (HNO97) in vitro, using network pharmacology, biological verification, and phytochemical analysis. Methods The study included UPLC-ESI–MS/MS analysis, cytotoxicity assays, cell cycle analysis, apoptosis assessment, and RT-qPCR for gene expression of Bcl2, p53, and ATG7. Potential targets were identified, and mechanisms of action were examined through online databases and enrichment analyses. Results The R. dentatus L. extract contained 14 phenolic aglycons. Combining cisplatin and R. dentatus L. was more effective in inhibiting proliferation, inducing cell cycle arrest and apoptosis, and reducing autophagy in HNO97 cells than cisplatin alone. KEGG analysis indicated that the drug combination might work through pathways like PI3K-Akt signaling, microRNAs in cancer, and EGFR tyrosine kinase inhibitor resistance. Conclusions Combining cisplatin with R. dentatus L. may be a promising approach for treating tongue carcinoma by affecting multiple pathways, providing a new perspective for developing more effective treatments for OSCC.
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spelling doaj-art-c120c4f50f6b44ef942bacb2d44c1dba2025-01-26T12:15:12ZengBMCBMC Complementary Medicine and Therapies2662-76712025-01-0125112810.1186/s12906-024-04718-5Synergistic anticancer effects of cisplatin and phenolic aglycones of the aerial part of Rumex dentatus L. in tongue squamous cell carcinoma: insights from network pharmacology and biological verificationAmany E. Ragab0Ghada M. Al-Ashmawy1Sherin R. El Afify2Ola A. El-Feky3Amera O. Ibrahim4Department of Pharmacognosy, Faculty of Pharmacy, Tanta UniversityDepartment of Biochemistry, Faculty of Pharmacy, Tanta UniversityDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Alsalam UniversityDepartment of Biochemistry, Faculty of Pharmacy, Tanta UniversityDepartment of Biochemistry, Faculty of Pharmacy, Tanta UniversityAbstract Background Oral squamous cell carcinoma (OSCC) ranks as the sixth most common malignancy globally. Cisplatin is the standard chemotherapy for OSCC, but resistance often reduces its efficacy, necessitating new treatments with fewer side effects. Rumex dentatus L., from the Polygonaceae family, is known for its medicinal properties, but its anticancer potential has not been thoroughly explored. This study aimed to investigate the synergy between cisplatin and an extract from the aerial parts of R. dentatus L. in treating tongue carcinoma (HNO97) in vitro, using network pharmacology, biological verification, and phytochemical analysis. Methods The study included UPLC-ESI–MS/MS analysis, cytotoxicity assays, cell cycle analysis, apoptosis assessment, and RT-qPCR for gene expression of Bcl2, p53, and ATG7. Potential targets were identified, and mechanisms of action were examined through online databases and enrichment analyses. Results The R. dentatus L. extract contained 14 phenolic aglycons. Combining cisplatin and R. dentatus L. was more effective in inhibiting proliferation, inducing cell cycle arrest and apoptosis, and reducing autophagy in HNO97 cells than cisplatin alone. KEGG analysis indicated that the drug combination might work through pathways like PI3K-Akt signaling, microRNAs in cancer, and EGFR tyrosine kinase inhibitor resistance. Conclusions Combining cisplatin with R. dentatus L. may be a promising approach for treating tongue carcinoma by affecting multiple pathways, providing a new perspective for developing more effective treatments for OSCC.https://doi.org/10.1186/s12906-024-04718-5Oral Squamous Cell Carcinoma (OSCC)Rumex dentatus L.Cisplatin ResistanceApoptosisCell Cycle ArrestNetwork Pharmacology
spellingShingle Amany E. Ragab
Ghada M. Al-Ashmawy
Sherin R. El Afify
Ola A. El-Feky
Amera O. Ibrahim
Synergistic anticancer effects of cisplatin and phenolic aglycones of the aerial part of Rumex dentatus L. in tongue squamous cell carcinoma: insights from network pharmacology and biological verification
BMC Complementary Medicine and Therapies
Oral Squamous Cell Carcinoma (OSCC)
Rumex dentatus L.
Cisplatin Resistance
Apoptosis
Cell Cycle Arrest
Network Pharmacology
title Synergistic anticancer effects of cisplatin and phenolic aglycones of the aerial part of Rumex dentatus L. in tongue squamous cell carcinoma: insights from network pharmacology and biological verification
title_full Synergistic anticancer effects of cisplatin and phenolic aglycones of the aerial part of Rumex dentatus L. in tongue squamous cell carcinoma: insights from network pharmacology and biological verification
title_fullStr Synergistic anticancer effects of cisplatin and phenolic aglycones of the aerial part of Rumex dentatus L. in tongue squamous cell carcinoma: insights from network pharmacology and biological verification
title_full_unstemmed Synergistic anticancer effects of cisplatin and phenolic aglycones of the aerial part of Rumex dentatus L. in tongue squamous cell carcinoma: insights from network pharmacology and biological verification
title_short Synergistic anticancer effects of cisplatin and phenolic aglycones of the aerial part of Rumex dentatus L. in tongue squamous cell carcinoma: insights from network pharmacology and biological verification
title_sort synergistic anticancer effects of cisplatin and phenolic aglycones of the aerial part of rumex dentatus l in tongue squamous cell carcinoma insights from network pharmacology and biological verification
topic Oral Squamous Cell Carcinoma (OSCC)
Rumex dentatus L.
Cisplatin Resistance
Apoptosis
Cell Cycle Arrest
Network Pharmacology
url https://doi.org/10.1186/s12906-024-04718-5
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