Cytotoxicity and Radiosensitizing Potentials of Pilosulin-3, a Recombinant Ant Venom, in Breast Cancer Cells
Venom peptides are promising agents in the development of unconventional anticancer therapeutic agents. This study explored the potential of Pilosulin-3, a recombinant peptide from the venom of the Australian jack jumper ant “<i>Myrmecia pilosula</i>”, as a cytotoxic and radiosensitizing...
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MDPI AG
2023-12-01
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| Series: | Toxins |
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| Online Access: | https://www.mdpi.com/2072-6651/15/12/701 |
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| author | Reema M. Alzeer Khaled S. Al-Hadyan Najla M. Al-Harbi Sara S. Bin Judia Rafa S. Almeer Ghazi A. Alsbeih |
| author_facet | Reema M. Alzeer Khaled S. Al-Hadyan Najla M. Al-Harbi Sara S. Bin Judia Rafa S. Almeer Ghazi A. Alsbeih |
| author_sort | Reema M. Alzeer |
| collection | DOAJ |
| description | Venom peptides are promising agents in the development of unconventional anticancer therapeutic agents. This study explored the potential of Pilosulin-3, a recombinant peptide from the venom of the Australian jack jumper ant “<i>Myrmecia pilosula</i>”, as a cytotoxic and radiosensitizing agent in MCF-7 and MDA-MB-231 breast cancer (BC) cell lines. Pilosulin-3’s cytotoxicity was evaluated across a wide range of concentrations using a proliferation assay. Cell cycle progression and apoptosis were examined at the inhibitory concentration 25% (IC25) and IC50 of Pilosulin-3, both with and without a 4Gy X-ray irradiation dose. Radiosensitivity was assessed at IC25 using the clonogenic survival assay. The study revealed that Pilosulin-3 exerted a concentration-dependent cytotoxic effect, with IC25 and IC50 values of 0.01 and 0.5 µM, respectively. In silico screening indicated high selectivity of Pilosulin-3 peptide, which was predicted to be the most likely anticancer agent (PROB = 0.997) with low hemolytic activity (PROP = 0.176). Although Pilosulin-3 exhibited a significant (<i>p</i> < 0.05) G2/M cell cycle arrest in combination with radiation, there was no discernible effect on apoptosis induction or cell survival following irradiation. In conclusion, Pilosulin-3 proved to be cytotoxic to BC cells and induced a cytostatic effect (G2/M arrest) when combined with radiation. However, it did not enhance the efficacy of cell killing by irradiation. While it holds potential as a cytotoxic agent in breast cancer treatment, its application as a radiosensitizer does not find support in these results. |
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| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-03-08T20:18:59Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-4558f2f11a5840fcb217bd8a5a4387df2023-12-22T14:46:19ZengMDPI AGToxins2072-66512023-12-01151270110.3390/toxins15120701Cytotoxicity and Radiosensitizing Potentials of Pilosulin-3, a Recombinant Ant Venom, in Breast Cancer CellsReema M. Alzeer0Khaled S. Al-Hadyan1Najla M. Al-Harbi2Sara S. Bin Judia3Rafa S. Almeer4Ghazi A. Alsbeih5Department of Zoology, College of Science, King Saud University, Riyadh 11541, Saudi ArabiaBiomedical Physics Department, Radiation Biology Section, King Faisal Specialist Hospital & Research Centre, Riyadh 11211, Saudi ArabiaBiomedical Physics Department, Radiation Biology Section, King Faisal Specialist Hospital & Research Centre, Riyadh 11211, Saudi ArabiaBiomedical Physics Department, Radiation Biology Section, King Faisal Specialist Hospital & Research Centre, Riyadh 11211, Saudi ArabiaDepartment of Zoology, College of Science, King Saud University, Riyadh 11541, Saudi ArabiaBiomedical Physics Department, Radiation Biology Section, King Faisal Specialist Hospital & Research Centre, Riyadh 11211, Saudi ArabiaVenom peptides are promising agents in the development of unconventional anticancer therapeutic agents. This study explored the potential of Pilosulin-3, a recombinant peptide from the venom of the Australian jack jumper ant “<i>Myrmecia pilosula</i>”, as a cytotoxic and radiosensitizing agent in MCF-7 and MDA-MB-231 breast cancer (BC) cell lines. Pilosulin-3’s cytotoxicity was evaluated across a wide range of concentrations using a proliferation assay. Cell cycle progression and apoptosis were examined at the inhibitory concentration 25% (IC25) and IC50 of Pilosulin-3, both with and without a 4Gy X-ray irradiation dose. Radiosensitivity was assessed at IC25 using the clonogenic survival assay. The study revealed that Pilosulin-3 exerted a concentration-dependent cytotoxic effect, with IC25 and IC50 values of 0.01 and 0.5 µM, respectively. In silico screening indicated high selectivity of Pilosulin-3 peptide, which was predicted to be the most likely anticancer agent (PROB = 0.997) with low hemolytic activity (PROP = 0.176). Although Pilosulin-3 exhibited a significant (<i>p</i> < 0.05) G2/M cell cycle arrest in combination with radiation, there was no discernible effect on apoptosis induction or cell survival following irradiation. In conclusion, Pilosulin-3 proved to be cytotoxic to BC cells and induced a cytostatic effect (G2/M arrest) when combined with radiation. However, it did not enhance the efficacy of cell killing by irradiation. While it holds potential as a cytotoxic agent in breast cancer treatment, its application as a radiosensitizer does not find support in these results.https://www.mdpi.com/2072-6651/15/12/701Pilosulin-3ant venomradiosensitizationcytotoxicitybreast cancer |
| spellingShingle | Reema M. Alzeer Khaled S. Al-Hadyan Najla M. Al-Harbi Sara S. Bin Judia Rafa S. Almeer Ghazi A. Alsbeih Cytotoxicity and Radiosensitizing Potentials of Pilosulin-3, a Recombinant Ant Venom, in Breast Cancer Cells Toxins Pilosulin-3 ant venom radiosensitization cytotoxicity breast cancer |
| title | Cytotoxicity and Radiosensitizing Potentials of Pilosulin-3, a Recombinant Ant Venom, in Breast Cancer Cells |
| title_full | Cytotoxicity and Radiosensitizing Potentials of Pilosulin-3, a Recombinant Ant Venom, in Breast Cancer Cells |
| title_fullStr | Cytotoxicity and Radiosensitizing Potentials of Pilosulin-3, a Recombinant Ant Venom, in Breast Cancer Cells |
| title_full_unstemmed | Cytotoxicity and Radiosensitizing Potentials of Pilosulin-3, a Recombinant Ant Venom, in Breast Cancer Cells |
| title_short | Cytotoxicity and Radiosensitizing Potentials of Pilosulin-3, a Recombinant Ant Venom, in Breast Cancer Cells |
| title_sort | cytotoxicity and radiosensitizing potentials of pilosulin 3 a recombinant ant venom in breast cancer cells |
| topic | Pilosulin-3 ant venom radiosensitization cytotoxicity breast cancer |
| url | https://www.mdpi.com/2072-6651/15/12/701 |
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