Cytotoxicity and Radiosensitizing Potentials of Pilosulin-3, a Recombinant Ant Venom, in Breast Cancer Cells

• Published in: Toxins Vol. 15; no. 12; p. 701
• Main Authors: Alzeer, Reema M, Al-Hadyan, Khaled S, Al-Harbi, Najla M, Bin Judia, Sara S, Almeer, Rafa S, Alsbeih, Ghazi A
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01-12-2023; MDPI
• Subjects: ant venom; Anticancer properties; Antimicrobial agents; Antitumor agents; Apoptosis; Breast cancer; Cancer; Cancer cells; Cancer therapies; Care and treatment; Cell cycle; Cell growth; Cell survival; Chemotherapy; Cytotoxicity; Drug dosages; Flow cytometry; Histamine; Insects; Irradiation; Peptides; Pharmacology; Physiological aspects; Pilosulin-3; Radiation; Radiation dosage; Radiosensitivity; radiosensitization; Radiosensitizers; Survival; Toxicity; Tumor cell lines; Venom; X ray irradiation; X-rays; Saudi Arabia; breast cancer; Pilosulin-3; cytotoxicity; radiosensitization; ant venom
• ISSN: 2072-6651; 2072-6651
• DOI: 10.3390/toxins15120701

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 "
", 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 (
< 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.