De Novo Design of AC-P19M, a Novel Anticancer Peptide with Apoptotic Effects on Lung Cancer Cells and Anti-Angiogenic Activity
Despite the current developments in cancer therapeutics, efforts to excavate new anticancer agents continue rigorously due to obstacles, such as side effects and drug resistance. Anticancer peptides (ACPs) can be utilized to treat cancer because of their effectiveness on a variety of molecular targe...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-12-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/23/24/15594 |
| _version_ | 1797457354022715392 |
|---|---|
| author | Min Kyoung Shin Bo-Young Jang Kyung-Bin Bu Seung-Ho Lee Dong-Hee Han Jin Wook Oh Jung-Suk Sung |
| author_facet | Min Kyoung Shin Bo-Young Jang Kyung-Bin Bu Seung-Ho Lee Dong-Hee Han Jin Wook Oh Jung-Suk Sung |
| author_sort | Min Kyoung Shin |
| collection | DOAJ |
| description | Despite the current developments in cancer therapeutics, efforts to excavate new anticancer agents continue rigorously due to obstacles, such as side effects and drug resistance. Anticancer peptides (ACPs) can be utilized to treat cancer because of their effectiveness on a variety of molecular targets, along with high selectivity and specificity for cancer cells. In the present study, a novel ACP was de novo designed using in silico methods, and its functionality and molecular mechanisms of action were explored. AC-P19M was discovered through functional prediction and sequence modification based on peptide sequences currently available in the database. The peptide exhibited anticancer activity against lung cancer cells, A549 and H460, by disrupting cellular membranes and inducing apoptosis while showing low toxicity towards normal and red blood cells. In addition, the peptide inhibited the migration and invasion of lung cancer cells and reversed epithelial-mesenchymal transition. Moreover, AC-P19M showed anti-angiogenic activity through the inhibition of vascular endothelial growth factor receptor 2 signaling. Our findings suggest that AC-P19M is a novel ACP that directly or indirectly targets cancer cells, demonstrating the potential development of an anticancer agent and providing insights into the discovery of functional substances based on an in silico approach. |
| first_indexed | 2024-03-09T16:20:02Z |
| format | Article |
| id | doaj.art-c499a2887193443494324a9d6124ee56 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T16:20:02Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-c499a2887193443494324a9d6124ee562023-11-24T15:24:15ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-12-0123241559410.3390/ijms232415594De Novo Design of AC-P19M, a Novel Anticancer Peptide with Apoptotic Effects on Lung Cancer Cells and Anti-Angiogenic ActivityMin Kyoung Shin0Bo-Young Jang1Kyung-Bin Bu2Seung-Ho Lee3Dong-Hee Han4Jin Wook Oh5Jung-Suk Sung6Department of Life Science, Dongguk University-Seoul, Goyang 10326, Republic of KoreaDepartment of Life Science, Dongguk University-Seoul, Goyang 10326, Republic of KoreaDepartment of Life Science, Dongguk University-Seoul, Goyang 10326, Republic of KoreaDepartment of Life Science, Dongguk University-Seoul, Goyang 10326, Republic of KoreaDepartment of Life Science, Dongguk University-Seoul, Goyang 10326, Republic of KoreaDepartment of Life Science, Dongguk University-Seoul, Goyang 10326, Republic of KoreaDepartment of Life Science, Dongguk University-Seoul, Goyang 10326, Republic of KoreaDespite the current developments in cancer therapeutics, efforts to excavate new anticancer agents continue rigorously due to obstacles, such as side effects and drug resistance. Anticancer peptides (ACPs) can be utilized to treat cancer because of their effectiveness on a variety of molecular targets, along with high selectivity and specificity for cancer cells. In the present study, a novel ACP was de novo designed using in silico methods, and its functionality and molecular mechanisms of action were explored. AC-P19M was discovered through functional prediction and sequence modification based on peptide sequences currently available in the database. The peptide exhibited anticancer activity against lung cancer cells, A549 and H460, by disrupting cellular membranes and inducing apoptosis while showing low toxicity towards normal and red blood cells. In addition, the peptide inhibited the migration and invasion of lung cancer cells and reversed epithelial-mesenchymal transition. Moreover, AC-P19M showed anti-angiogenic activity through the inhibition of vascular endothelial growth factor receptor 2 signaling. Our findings suggest that AC-P19M is a novel ACP that directly or indirectly targets cancer cells, demonstrating the potential development of an anticancer agent and providing insights into the discovery of functional substances based on an in silico approach.https://www.mdpi.com/1422-0067/23/24/15594anticancer peptide (ACP)in silico analysiscell lysisapoptosisEMT inhibitionanti-angiogenic |
| spellingShingle | Min Kyoung Shin Bo-Young Jang Kyung-Bin Bu Seung-Ho Lee Dong-Hee Han Jin Wook Oh Jung-Suk Sung De Novo Design of AC-P19M, a Novel Anticancer Peptide with Apoptotic Effects on Lung Cancer Cells and Anti-Angiogenic Activity International Journal of Molecular Sciences anticancer peptide (ACP) in silico analysis cell lysis apoptosis EMT inhibition anti-angiogenic |
| title | De Novo Design of AC-P19M, a Novel Anticancer Peptide with Apoptotic Effects on Lung Cancer Cells and Anti-Angiogenic Activity |
| title_full | De Novo Design of AC-P19M, a Novel Anticancer Peptide with Apoptotic Effects on Lung Cancer Cells and Anti-Angiogenic Activity |
| title_fullStr | De Novo Design of AC-P19M, a Novel Anticancer Peptide with Apoptotic Effects on Lung Cancer Cells and Anti-Angiogenic Activity |
| title_full_unstemmed | De Novo Design of AC-P19M, a Novel Anticancer Peptide with Apoptotic Effects on Lung Cancer Cells and Anti-Angiogenic Activity |
| title_short | De Novo Design of AC-P19M, a Novel Anticancer Peptide with Apoptotic Effects on Lung Cancer Cells and Anti-Angiogenic Activity |
| title_sort | de novo design of ac p19m a novel anticancer peptide with apoptotic effects on lung cancer cells and anti angiogenic activity |
| topic | anticancer peptide (ACP) in silico analysis cell lysis apoptosis EMT inhibition anti-angiogenic |
| url | https://www.mdpi.com/1422-0067/23/24/15594 |
| work_keys_str_mv | AT minkyoungshin denovodesignofacp19manovelanticancerpeptidewithapoptoticeffectsonlungcancercellsandantiangiogenicactivity AT boyoungjang denovodesignofacp19manovelanticancerpeptidewithapoptoticeffectsonlungcancercellsandantiangiogenicactivity AT kyungbinbu denovodesignofacp19manovelanticancerpeptidewithapoptoticeffectsonlungcancercellsandantiangiogenicactivity AT seungholee denovodesignofacp19manovelanticancerpeptidewithapoptoticeffectsonlungcancercellsandantiangiogenicactivity AT dongheehan denovodesignofacp19manovelanticancerpeptidewithapoptoticeffectsonlungcancercellsandantiangiogenicactivity AT jinwookoh denovodesignofacp19manovelanticancerpeptidewithapoptoticeffectsonlungcancercellsandantiangiogenicactivity AT jungsuksung denovodesignofacp19manovelanticancerpeptidewithapoptoticeffectsonlungcancercellsandantiangiogenicactivity |