Engineering BinB Pore-Forming Toxin for Selective Killing of Breast Cancer Cells
Issued Date
2023-04-01
Resource Type
eISSN
20726651
Scopus ID
2-s2.0-85153938816
Pubmed ID
37104235
Journal Title
Toxins
Volume
15
Issue
4
Rights Holder(s)
SCOPUS
Bibliographic Citation
Toxins Vol.15 No.4 (2023)
Suggested Citation
Kumkoon T., Noree C., Boonserm P. Engineering BinB Pore-Forming Toxin for Selective Killing of Breast Cancer Cells. Toxins Vol.15 No.4 (2023). doi:10.3390/toxins15040297 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/82199
Title
Engineering BinB Pore-Forming Toxin for Selective Killing of Breast Cancer Cells
Author(s)
Author's Affiliation
Other Contributor(s)
Abstract
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 Lysinibacillus sphaericus (Ls) by fusing a luteinizing hormone-releasing hormone (LHRH) peptide to its pore-forming domain (BinBC) to target MCF-7 breast cancer cells as opposed to human fibroblast cells (Hs68). The results showed that LHRH-BinBC inhibited MCF-7 cell proliferation in a dose-dependent manner while leaving Hs68 cells unaffected. BinBC, at any concentration tested, did not affect the proliferation of MCF-7 or Hs68 cells. In addition, the LHRH-BinBC toxin caused the efflux of the cytoplasmic enzyme lactate dehydrogenase (LDH), demonstrating the efficacy of the LHRH peptide in directing the BinBC toxin to damage the plasma membranes of MCF-7 cancer cells. LHRH-BinBC also caused MCF-7 cell apoptosis by activating caspase-8. In addition, LHRH-BinBC was predominantly observed on the cell surface of MCF-7 and Hs68 cells, without colocalization with mitochondria. Overall, our findings suggest that LHRH-BinBC could be investigated further as a potential cancer therapeutic agent.