Abstract
Animal venoms are rich sources for the discovery and development of new bioactive compounds. In the past decade, there are many promising studies in the literature on the usage and the development of new therapeutic approaches of snake venoms and their derivatives against various cancer types including breast and prostate cancers. Tarantula cubensis venom (Theranekron®) contains chemically complex digestive enzyme mixtures, is commercially available, and is broadly used as a therapeutic approach in clinical veterinary. However, there are very limited studies examining its molecular impact in human tumors. In the present study, we evaluated the biochemical effects of Theranekron on prostate cancer cells and its mechanism of action on molecular signal pathways. It was determined that androgen-sensitive prostate cancer cells, LNCaP, are more sensitive to Theranekron® than normal prostate cells (PNT1A) and epithelial metastatic prostatic cell (DU145). It also enhanced the autophagic activity and induced endoplasmic reticulum stress and ubiquitin-proteasome system. Also, it markedly increased apoptotic cell death–related protein levels in LNCaP cells. Furthermore, Theranekron® strongly reversed epithelial-mesenchymal transition of LNCaP cells and decreased cancer progression. Additionally, colonial growth of prostate cancer cells was significantly constrained with Theranekron treatment.
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Acknowledgements
We thank Suleyman Demirel University-Innovative Technologies Application and Research Center. Fluorescence microscopic monitoring was performed in Suleyman Demirel University, Medical School, Department of Pathology. We thank Dr. Onur ERTUNC.
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This study was supported by Suleyman Demirel University internal funds (TSG-2021- 8302, TAB-2020-8253).
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YE initiated and directed the project, designed, conducted the experiments, analyzed and interpreted the results, and wrote the manuscript. HKD, DC, and EA assisted with all experimental studies. All authors have done a critical revision of the manuscript and approved the final submission.
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Erzurumlu, Y., Dogan, H.K., Catakli, D. et al. Tarantula cubensis Extract Induces Cell Death in Prostate Cancer by Promoting Autophagic Flux/ER Stress Responses and Decreased Epithelial-Mesenchymal Transition. Rev. Bras. Farmacogn. 32, 575–582 (2022). https://doi.org/10.1007/s43450-022-00279-1
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DOI: https://doi.org/10.1007/s43450-022-00279-1