A Potent EGFR Inhibitor, N-Phenyl Pyrazoline Derivative Suppresses Aggressiveness and Cancer Stem Cell-Like Phenotype of Cervical Cancer Cells
Objective: Metastasis causes approximately 90% of cancer-related deaths, including in cervical cancer patients. Uncontrolled cell proliferation, migration, and cancer stemness act as critical events in primary tumor growth and cancer metastasis progression in cervical cancer. Here, we investigated...
| Main Authors: | , , , , , |
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| Format: | Other |
| Language: | English |
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Drug Design, Development and Therapy
2022
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| Online Access: | https://repository.ugm.ac.id/284222/1/A-Potent-EGFR-Inhibitor-NPhenyl-Pyrazoline-Derivative-Suppresses-Aggressiveness-and-Cancer-Stem-CellLike-Phenotype-of-Cervical-Cancer-CellsDrug-Design-Development-and-Therapy.pdf |
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| author | Mustofa, Mustofa Satriyo, Pamungkas Bagus Suma, Artania Adnin Tri Waskitha, Stephanus Satria Wira Wahyuningsih, Tutik Dwi Sholikhah, Eti Nurwening |
| author_facet | Mustofa, Mustofa Satriyo, Pamungkas Bagus Suma, Artania Adnin Tri Waskitha, Stephanus Satria Wira Wahyuningsih, Tutik Dwi Sholikhah, Eti Nurwening |
| author_sort | Mustofa, Mustofa |
| collection | UGM |
| description | Objective: Metastasis causes approximately 90% of cancer-related deaths, including in cervical cancer patients. Uncontrolled cell
proliferation, migration, and cancer stemness act as critical events in primary tumor growth and cancer metastasis progression in
cervical cancer. Here, we investigated the anti-proliferative, anti-migration, and cancer stemness inhibition activity of N-phenyl
pyrazoline derivatives against cervical cancer cells.
Methods: The chalcone and phenylhydrazine were used to synthesize the N-phenyl pyrazoline 2/5 (P2 and P5). The MTT, colony
formation, and wound healing assays were performed to evaluate the N-phenyl pyrazoline effect in HeLa cells. The N-phenyl
pyrazoline’s protein target was predicted using SwissTargetPrediction and AutoDock Vina software. The Western blotting assay
was performed to evaluate the target proteins. The public dataset analysis was used to confirm the clinical relevance of target protein in
cervical cancer patients.
Results: N-phenyl pyrazoline 2 and 5 were successfully synthesized. The N-phenyl pyrazolines 2 and 5 exhibit cytotoxic effect in
HeLa cell line with 20.26 µM, 4.708 µM of IC50, respectively. Further study shows that the N-phenyl pyrazoline 5 suppresses the cell
proliferation and migration ability of HeLa cell line in a dose-dependent manner. Target prediction and molecular docking reveal that
EGFR and ERBB2 protein as the main target of the N-phenyl pyrazoline 5 compound. The N-phenyl pyrazoline 5 suppresses the
EGFR expression level but not the total ERK1/2. Public data and GSEA analysis found that the EGFR high expression level is
positively associated with poor survival, cancer metastasis-related signaling pathways, and cancer stem cell markers in cervical cancer
patients. In addition, the N-phenyl pyrazoline 5 reduces the HeLa’s tumorsphere size and cancer stem cell marker, CD133.
Conclusion: N-phenyl pyrazoline 5 suppresses the cell viability, proliferation, migration, and cancer stem cell-like phenotype of
cervical cancer cells via EGFR inhibition. |
| first_indexed | 2024-03-14T00:09:43Z |
| format | Other |
| id | oai:generic.eprints.org:284222 |
| institution | Universiti Gadjah Mada |
| language | English |
| last_indexed | 2024-03-14T00:09:43Z |
| publishDate | 2022 |
| publisher | Drug Design, Development and Therapy |
| record_format | dspace |
| spelling | oai:generic.eprints.org:2842222023-11-29T08:15:49Z https://repository.ugm.ac.id/284222/ A Potent EGFR Inhibitor, N-Phenyl Pyrazoline Derivative Suppresses Aggressiveness and Cancer Stem Cell-Like Phenotype of Cervical Cancer Cells Mustofa, Mustofa Satriyo, Pamungkas Bagus Suma, Artania Adnin Tri Waskitha, Stephanus Satria Wira Wahyuningsih, Tutik Dwi Sholikhah, Eti Nurwening Medicinal and Biomolecular Chemistry Objective: Metastasis causes approximately 90% of cancer-related deaths, including in cervical cancer patients. Uncontrolled cell proliferation, migration, and cancer stemness act as critical events in primary tumor growth and cancer metastasis progression in cervical cancer. Here, we investigated the anti-proliferative, anti-migration, and cancer stemness inhibition activity of N-phenyl pyrazoline derivatives against cervical cancer cells. Methods: The chalcone and phenylhydrazine were used to synthesize the N-phenyl pyrazoline 2/5 (P2 and P5). The MTT, colony formation, and wound healing assays were performed to evaluate the N-phenyl pyrazoline effect in HeLa cells. The N-phenyl pyrazoline’s protein target was predicted using SwissTargetPrediction and AutoDock Vina software. The Western blotting assay was performed to evaluate the target proteins. The public dataset analysis was used to confirm the clinical relevance of target protein in cervical cancer patients. Results: N-phenyl pyrazoline 2 and 5 were successfully synthesized. The N-phenyl pyrazolines 2 and 5 exhibit cytotoxic effect in HeLa cell line with 20.26 µM, 4.708 µM of IC50, respectively. Further study shows that the N-phenyl pyrazoline 5 suppresses the cell proliferation and migration ability of HeLa cell line in a dose-dependent manner. Target prediction and molecular docking reveal that EGFR and ERBB2 protein as the main target of the N-phenyl pyrazoline 5 compound. The N-phenyl pyrazoline 5 suppresses the EGFR expression level but not the total ERK1/2. Public data and GSEA analysis found that the EGFR high expression level is positively associated with poor survival, cancer metastasis-related signaling pathways, and cancer stem cell markers in cervical cancer patients. In addition, the N-phenyl pyrazoline 5 reduces the HeLa’s tumorsphere size and cancer stem cell marker, CD133. Conclusion: N-phenyl pyrazoline 5 suppresses the cell viability, proliferation, migration, and cancer stem cell-like phenotype of cervical cancer cells via EGFR inhibition. Drug Design, Development and Therapy 2022 Other NonPeerReviewed application/pdf en https://repository.ugm.ac.id/284222/1/A-Potent-EGFR-Inhibitor-NPhenyl-Pyrazoline-Derivative-Suppresses-Aggressiveness-and-Cancer-Stem-CellLike-Phenotype-of-Cervical-Cancer-CellsDrug-Design-Development-and-Therapy.pdf Mustofa, Mustofa and Satriyo, Pamungkas Bagus and Suma, Artania Adnin Tri and Waskitha, Stephanus Satria Wira and Wahyuningsih, Tutik Dwi and Sholikhah, Eti Nurwening (2022) A Potent EGFR Inhibitor, N-Phenyl Pyrazoline Derivative Suppresses Aggressiveness and Cancer Stem Cell-Like Phenotype of Cervical Cancer Cells. Drug Design, Development and Therapy. https://pubmed.ncbi.nlm.nih.gov/35899233/ 10.2147/DDDT.S350913 |
| spellingShingle | Medicinal and Biomolecular Chemistry Mustofa, Mustofa Satriyo, Pamungkas Bagus Suma, Artania Adnin Tri Waskitha, Stephanus Satria Wira Wahyuningsih, Tutik Dwi Sholikhah, Eti Nurwening A Potent EGFR Inhibitor, N-Phenyl Pyrazoline Derivative Suppresses Aggressiveness and Cancer Stem Cell-Like Phenotype of Cervical Cancer Cells |
| title | A Potent EGFR Inhibitor, N-Phenyl Pyrazoline
Derivative Suppresses Aggressiveness and Cancer
Stem Cell-Like Phenotype of Cervical Cancer Cells |
| title_full | A Potent EGFR Inhibitor, N-Phenyl Pyrazoline
Derivative Suppresses Aggressiveness and Cancer
Stem Cell-Like Phenotype of Cervical Cancer Cells |
| title_fullStr | A Potent EGFR Inhibitor, N-Phenyl Pyrazoline
Derivative Suppresses Aggressiveness and Cancer
Stem Cell-Like Phenotype of Cervical Cancer Cells |
| title_full_unstemmed | A Potent EGFR Inhibitor, N-Phenyl Pyrazoline
Derivative Suppresses Aggressiveness and Cancer
Stem Cell-Like Phenotype of Cervical Cancer Cells |
| title_short | A Potent EGFR Inhibitor, N-Phenyl Pyrazoline
Derivative Suppresses Aggressiveness and Cancer
Stem Cell-Like Phenotype of Cervical Cancer Cells |
| title_sort | potent egfr inhibitor n phenyl pyrazoline derivative suppresses aggressiveness and cancer stem cell like phenotype of cervical cancer cells |
| topic | Medicinal and Biomolecular Chemistry |
| url | https://repository.ugm.ac.id/284222/1/A-Potent-EGFR-Inhibitor-NPhenyl-Pyrazoline-Derivative-Suppresses-Aggressiveness-and-Cancer-Stem-CellLike-Phenotype-of-Cervical-Cancer-CellsDrug-Design-Development-and-Therapy.pdf |
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