Novel Hybrids of Podophyllotoxin and Coumarin Inhibit the Growth and Migration of Human Oral Squamous Carcinoma Cells
Oral squamous cell carcinoma is the most common malignancy of oral tumor. In this study, two novel hybrids of podophyllotoxin and coumarin were designed using molecular hybridization strategy and synthesized. Pharmacological evaluation showed that the potent compound 12b inhibited the proliferation...
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Frontiers Media S.A.
2021-01-01
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| Series: | Frontiers in Chemistry |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fchem.2020.626075/full |
| _version_ | 1819298818641887232 |
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| author | Guohui Bai Dan Zhao Xin Ran Lei Zhang Degang Zhao Degang Zhao |
| author_facet | Guohui Bai Dan Zhao Xin Ran Lei Zhang Degang Zhao Degang Zhao |
| author_sort | Guohui Bai |
| collection | DOAJ |
| description | Oral squamous cell carcinoma is the most common malignancy of oral tumor. In this study, two novel hybrids of podophyllotoxin and coumarin were designed using molecular hybridization strategy and synthesized. Pharmacological evaluation showed that the potent compound 12b inhibited the proliferation of three human oral squamous carcinoma cell lines with nanomolar IC50 values, as well as displayed less toxicity on normal cells. Mechanistic studies indicated that 12b triggered HSC-2 cell apoptosis, induced cell cycle arrest, and inhibited cell migration. Moreover, 12b could disturb the microtubule network via binding into the tubulin. It was noteworthy that induction of autophagy by 12b was associated with the upregulation of Beclin1, as well as LC3-II. Furthermore, 12b significantly stimulated the AMPK pathway and restrained the AKT/mTOR pathway in HSC-2 cells. These results indicated that compound 12b was a promising candidate for further investigation. |
| first_indexed | 2024-12-24T05:35:57Z |
| format | Article |
| id | doaj.art-876029cee03f442dba3e3c462acf2e59 |
| institution | Directory Open Access Journal |
| issn | 2296-2646 |
| language | English |
| last_indexed | 2024-12-24T05:35:57Z |
| publishDate | 2021-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Chemistry |
| spelling | doaj.art-876029cee03f442dba3e3c462acf2e592022-12-21T17:13:01ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462021-01-01810.3389/fchem.2020.626075626075Novel Hybrids of Podophyllotoxin and Coumarin Inhibit the Growth and Migration of Human Oral Squamous Carcinoma CellsGuohui Bai0Dan Zhao1Xin Ran2Lei Zhang3Degang Zhao4Degang Zhao5The Key Laboratory of Plant Resources Conservation and Germplasm Innovation in Mountainous Region (Ministry of Education), Institute of Agro-Bioengineering and College of Life Sciences, Guizhou University, Guiyang, ChinaThe Key Laboratory of Plant Resources Conservation and Germplasm Innovation in Mountainous Region (Ministry of Education), Institute of Agro-Bioengineering and College of Life Sciences, Guizhou University, Guiyang, ChinaThe Key Laboratory of Plant Resources Conservation and Germplasm Innovation in Mountainous Region (Ministry of Education), Institute of Agro-Bioengineering and College of Life Sciences, Guizhou University, Guiyang, ChinaKey Laboratory of Biocatalysis & Chiral Drug Synthesis of Guizhou Province and School of Pharmacy, Zunyi Medical University, Zunyi, ChinaThe Key Laboratory of Plant Resources Conservation and Germplasm Innovation in Mountainous Region (Ministry of Education), Institute of Agro-Bioengineering and College of Life Sciences, Guizhou University, Guiyang, ChinaInstitute of Guizhou Distinctive Plant Resources Conservation, Guizhou Academy of Agricultural Science, Guiyang, ChinaOral squamous cell carcinoma is the most common malignancy of oral tumor. In this study, two novel hybrids of podophyllotoxin and coumarin were designed using molecular hybridization strategy and synthesized. Pharmacological evaluation showed that the potent compound 12b inhibited the proliferation of three human oral squamous carcinoma cell lines with nanomolar IC50 values, as well as displayed less toxicity on normal cells. Mechanistic studies indicated that 12b triggered HSC-2 cell apoptosis, induced cell cycle arrest, and inhibited cell migration. Moreover, 12b could disturb the microtubule network via binding into the tubulin. It was noteworthy that induction of autophagy by 12b was associated with the upregulation of Beclin1, as well as LC3-II. Furthermore, 12b significantly stimulated the AMPK pathway and restrained the AKT/mTOR pathway in HSC-2 cells. These results indicated that compound 12b was a promising candidate for further investigation.https://www.frontiersin.org/articles/10.3389/fchem.2020.626075/fullpodophyllotoxincoumarinhybrid strategyhuman oral squamous carcinoma cellsanticancermolecular mechanism |
| spellingShingle | Guohui Bai Dan Zhao Xin Ran Lei Zhang Degang Zhao Degang Zhao Novel Hybrids of Podophyllotoxin and Coumarin Inhibit the Growth and Migration of Human Oral Squamous Carcinoma Cells Frontiers in Chemistry podophyllotoxin coumarin hybrid strategy human oral squamous carcinoma cells anticancer molecular mechanism |
| title | Novel Hybrids of Podophyllotoxin and Coumarin Inhibit the Growth and Migration of Human Oral Squamous Carcinoma Cells |
| title_full | Novel Hybrids of Podophyllotoxin and Coumarin Inhibit the Growth and Migration of Human Oral Squamous Carcinoma Cells |
| title_fullStr | Novel Hybrids of Podophyllotoxin and Coumarin Inhibit the Growth and Migration of Human Oral Squamous Carcinoma Cells |
| title_full_unstemmed | Novel Hybrids of Podophyllotoxin and Coumarin Inhibit the Growth and Migration of Human Oral Squamous Carcinoma Cells |
| title_short | Novel Hybrids of Podophyllotoxin and Coumarin Inhibit the Growth and Migration of Human Oral Squamous Carcinoma Cells |
| title_sort | novel hybrids of podophyllotoxin and coumarin inhibit the growth and migration of human oral squamous carcinoma cells |
| topic | podophyllotoxin coumarin hybrid strategy human oral squamous carcinoma cells anticancer molecular mechanism |
| url | https://www.frontiersin.org/articles/10.3389/fchem.2020.626075/full |
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