Inhibition of Prostate Cancer Cells by 4,5-Dicaffeoylquinic Acid through Cell Cycle Arrest
Prostate cancer is a major cause of cancer-related mortality in men. Even though current therapeutic management has contributed to reducing mortality, additional intervention strategies are warranted to further improve the outcomes. To this end, we have investigated the efficacy of dicaffeoylquinic...
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| Format: | Article |
| Language: | English |
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Wiley
2019-01-01
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| Series: | Prostate Cancer |
| Online Access: | http://dx.doi.org/10.1155/2019/4520645 |
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| author | Olivia Lodise Ketki Patil Igor Karshenboym Scott Prombo Chidinma Chukwueke S. Balakrishna Pai |
| author_facet | Olivia Lodise Ketki Patil Igor Karshenboym Scott Prombo Chidinma Chukwueke S. Balakrishna Pai |
| author_sort | Olivia Lodise |
| collection | DOAJ |
| description | Prostate cancer is a major cause of cancer-related mortality in men. Even though current therapeutic management has contributed to reducing mortality, additional intervention strategies are warranted to further improve the outcomes. To this end, we have investigated the efficacy of dicaffeoylquinic acids, ingredients in Yerba Mate (Ilex paraguariensis), an evergreen cultivated in South America, the leaves of which are used to prepare a tea/coffee-like drink. Of the various analogs tested, 4,5-dicaffeoylquinic acid (4,5-diCQA) was the most active molecule against DU-145 prostate cancer cells with a 50% inhibitory concentration (IC50) of 5 μM. 4,5-diCQA was active both under normoxic and hypoxic conditions. The effect of 72-hour treatment on DU-145 cells persisted for an extended time period as assessed by clonogenic assay. Mechanistic studies revealed that the toxic effect was not due to induction of programmed cell death but through cell cycle arrest at S phase. Additionally, 4,5-diCQA did not impact PI3K/MAPK signaling pathway nor did it affect the depolarization of the mitochondrial membrane. 4,5-diCQA-induced accumulation of cells in the S-phase also seems to negatively impact Bcl-2 expression. 4,5-diCQA also exhibited inhibitory activity on LNCaP and PC-3 prostate cancer cells suggesting that it has therapeutic potential on a broad range of prostate cancers. Taken together, the novel inhibitory activity and mechanism of action of 4,5-diCQA opens up potential therapeutic options for using this molecule as monotherapy as well as in combinatorial therapies for the clinical management of prostate cancer. |
| format | Article |
| id | doaj-art-e4cdf575c617414d9cadaa6f6d12b86b |
| institution | Kabale University |
| issn | 2090-3111 2090-312X |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Prostate Cancer |
| spelling | doaj-art-e4cdf575c617414d9cadaa6f6d12b86b2025-08-20T03:26:26ZengWileyProstate Cancer2090-31112090-312X2019-01-01201910.1155/2019/45206454520645Inhibition of Prostate Cancer Cells by 4,5-Dicaffeoylquinic Acid through Cell Cycle ArrestOlivia Lodise0Ketki Patil1Igor Karshenboym2Scott Prombo3Chidinma Chukwueke4S. Balakrishna Pai5Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, 313 Ferst Drive, Atlanta, Georgia 30332, USAWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, 313 Ferst Drive, Atlanta, Georgia 30332, USAWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, 313 Ferst Drive, Atlanta, Georgia 30332, USAWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, 313 Ferst Drive, Atlanta, Georgia 30332, USAWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, 313 Ferst Drive, Atlanta, Georgia 30332, USAWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, 313 Ferst Drive, Atlanta, Georgia 30332, USAProstate cancer is a major cause of cancer-related mortality in men. Even though current therapeutic management has contributed to reducing mortality, additional intervention strategies are warranted to further improve the outcomes. To this end, we have investigated the efficacy of dicaffeoylquinic acids, ingredients in Yerba Mate (Ilex paraguariensis), an evergreen cultivated in South America, the leaves of which are used to prepare a tea/coffee-like drink. Of the various analogs tested, 4,5-dicaffeoylquinic acid (4,5-diCQA) was the most active molecule against DU-145 prostate cancer cells with a 50% inhibitory concentration (IC50) of 5 μM. 4,5-diCQA was active both under normoxic and hypoxic conditions. The effect of 72-hour treatment on DU-145 cells persisted for an extended time period as assessed by clonogenic assay. Mechanistic studies revealed that the toxic effect was not due to induction of programmed cell death but through cell cycle arrest at S phase. Additionally, 4,5-diCQA did not impact PI3K/MAPK signaling pathway nor did it affect the depolarization of the mitochondrial membrane. 4,5-diCQA-induced accumulation of cells in the S-phase also seems to negatively impact Bcl-2 expression. 4,5-diCQA also exhibited inhibitory activity on LNCaP and PC-3 prostate cancer cells suggesting that it has therapeutic potential on a broad range of prostate cancers. Taken together, the novel inhibitory activity and mechanism of action of 4,5-diCQA opens up potential therapeutic options for using this molecule as monotherapy as well as in combinatorial therapies for the clinical management of prostate cancer.http://dx.doi.org/10.1155/2019/4520645 |
| spellingShingle | Olivia Lodise Ketki Patil Igor Karshenboym Scott Prombo Chidinma Chukwueke S. Balakrishna Pai Inhibition of Prostate Cancer Cells by 4,5-Dicaffeoylquinic Acid through Cell Cycle Arrest Prostate Cancer |
| title | Inhibition of Prostate Cancer Cells by 4,5-Dicaffeoylquinic Acid through Cell Cycle Arrest |
| title_full | Inhibition of Prostate Cancer Cells by 4,5-Dicaffeoylquinic Acid through Cell Cycle Arrest |
| title_fullStr | Inhibition of Prostate Cancer Cells by 4,5-Dicaffeoylquinic Acid through Cell Cycle Arrest |
| title_full_unstemmed | Inhibition of Prostate Cancer Cells by 4,5-Dicaffeoylquinic Acid through Cell Cycle Arrest |
| title_short | Inhibition of Prostate Cancer Cells by 4,5-Dicaffeoylquinic Acid through Cell Cycle Arrest |
| title_sort | inhibition of prostate cancer cells by 4 5 dicaffeoylquinic acid through cell cycle arrest |
| url | http://dx.doi.org/10.1155/2019/4520645 |
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