Engineering BinB Pore-Forming Toxin for Selective Killing of Breast Cancer Cells
Breast cancer is one of the most common cancers in women worldwide. Conventional cancer chemotherapy always has adverse side effects on the patient’s healthy tissues. Consequently, combining pore-forming toxins with cell-targeting peptides (CTPs) is a promising anticancer strategy for selectively de...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-04-01
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| Series: | Toxins |
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| Online Access: | https://www.mdpi.com/2072-6651/15/4/297 |
| _version_ | 1797603300368973824 |
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| author | Tipaporn Kumkoon Chalongrat Noree Panadda Boonserm |
| author_facet | Tipaporn Kumkoon Chalongrat Noree Panadda Boonserm |
| author_sort | Tipaporn Kumkoon |
| collection | DOAJ |
| description | Breast cancer is one of the most common cancers in women worldwide. Conventional cancer chemotherapy always has adverse side effects on the patient’s healthy tissues. Consequently, combining pore-forming toxins with cell-targeting peptides (CTPs) is a promising anticancer strategy for selectively destroying cancer cells. Here, we aim to improve the target specificity of the BinB toxin produced from <i>Lysinibacillus sphaericus</i> (Ls) by fusing a luteinizing hormone-releasing hormone (LHRH) peptide to its pore-forming domain (BinB<sub>C</sub>) to target MCF-7 breast cancer cells as opposed to human fibroblast cells (Hs68). The results showed that LHRH-BinB<sub>C</sub> inhibited MCF-7 cell proliferation in a dose-dependent manner while leaving Hs68 cells unaffected. BinB<sub>C</sub>, at any concentration tested, did not affect the proliferation of MCF-7 or Hs68 cells. In addition, the LHRH-BinB<sub>C</sub> toxin caused the efflux of the cytoplasmic enzyme lactate dehydrogenase (LDH), demonstrating the efficacy of the LHRH peptide in directing the BinB<sub>C</sub> toxin to damage the plasma membranes of MCF-7 cancer cells. LHRH-BinB<sub>C</sub> also caused MCF-7 cell apoptosis by activating caspase-8. In addition, LHRH-BinB<sub>C</sub> was predominantly observed on the cell surface of MCF-7 and Hs68 cells, without colocalization with mitochondria. Overall, our findings suggest that LHRH-BinB<sub>C</sub> could be investigated further as a potential cancer therapeutic agent. |
| first_indexed | 2024-03-11T04:28:14Z |
| format | Article |
| id | doaj.art-947274fca4104cbdb4162d0526953293 |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-03-11T04:28:14Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-947274fca4104cbdb4162d05269532932023-11-17T21:39:12ZengMDPI AGToxins2072-66512023-04-0115429710.3390/toxins15040297Engineering BinB Pore-Forming Toxin for Selective Killing of Breast Cancer CellsTipaporn Kumkoon0Chalongrat Noree1Panadda Boonserm2Institute of Molecular Biosciences, Mahidol University, Salaya, Phuttamonthon, Nakhon Pathom 73170, ThailandInstitute of Molecular Biosciences, Mahidol University, Salaya, Phuttamonthon, Nakhon Pathom 73170, ThailandInstitute of Molecular Biosciences, Mahidol University, Salaya, Phuttamonthon, Nakhon Pathom 73170, ThailandBreast cancer is one of the most common cancers in women worldwide. Conventional cancer chemotherapy always has adverse side effects on the patient’s healthy tissues. Consequently, combining pore-forming toxins with cell-targeting peptides (CTPs) is a promising anticancer strategy for selectively destroying cancer cells. Here, we aim to improve the target specificity of the BinB toxin produced from <i>Lysinibacillus sphaericus</i> (Ls) by fusing a luteinizing hormone-releasing hormone (LHRH) peptide to its pore-forming domain (BinB<sub>C</sub>) to target MCF-7 breast cancer cells as opposed to human fibroblast cells (Hs68). The results showed that LHRH-BinB<sub>C</sub> inhibited MCF-7 cell proliferation in a dose-dependent manner while leaving Hs68 cells unaffected. BinB<sub>C</sub>, at any concentration tested, did not affect the proliferation of MCF-7 or Hs68 cells. In addition, the LHRH-BinB<sub>C</sub> toxin caused the efflux of the cytoplasmic enzyme lactate dehydrogenase (LDH), demonstrating the efficacy of the LHRH peptide in directing the BinB<sub>C</sub> toxin to damage the plasma membranes of MCF-7 cancer cells. LHRH-BinB<sub>C</sub> also caused MCF-7 cell apoptosis by activating caspase-8. In addition, LHRH-BinB<sub>C</sub> was predominantly observed on the cell surface of MCF-7 and Hs68 cells, without colocalization with mitochondria. Overall, our findings suggest that LHRH-BinB<sub>C</sub> could be investigated further as a potential cancer therapeutic agent.https://www.mdpi.com/2072-6651/15/4/297pore-forming toxin<i>Lysinibacillus sphaericus</i>cell-targeting peptidebreast cancer cellscell death |
| spellingShingle | Tipaporn Kumkoon Chalongrat Noree Panadda Boonserm Engineering BinB Pore-Forming Toxin for Selective Killing of Breast Cancer Cells Toxins pore-forming toxin <i>Lysinibacillus sphaericus</i> cell-targeting peptide breast cancer cells cell death |
| title | Engineering BinB Pore-Forming Toxin for Selective Killing of Breast Cancer Cells |
| title_full | Engineering BinB Pore-Forming Toxin for Selective Killing of Breast Cancer Cells |
| title_fullStr | Engineering BinB Pore-Forming Toxin for Selective Killing of Breast Cancer Cells |
| title_full_unstemmed | Engineering BinB Pore-Forming Toxin for Selective Killing of Breast Cancer Cells |
| title_short | Engineering BinB Pore-Forming Toxin for Selective Killing of Breast Cancer Cells |
| title_sort | engineering binb pore forming toxin for selective killing of breast cancer cells |
| topic | pore-forming toxin <i>Lysinibacillus sphaericus</i> cell-targeting peptide breast cancer cells cell death |
| url | https://www.mdpi.com/2072-6651/15/4/297 |
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