Ivermectin Synergizes with Modulated Electro-hyperthermia and Improves Its Anticancer Effects in a Triple-Negative Breast Cancer Mouse Model.

Autor:	Aloss K; Institute of Translational Medicine, Semmelweis University, Üllői út 26., Budapest 1085, Hungary.; Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest 1089, Hungary., Leroy Viana PH; Institute of Translational Medicine, Semmelweis University, Üllői út 26., Budapest 1085, Hungary., Bokhari SMZ; Institute of Translational Medicine, Semmelweis University, Üllői út 26., Budapest 1085, Hungary., Giunashvili N; Institute of Translational Medicine, Semmelweis University, Üllői út 26., Budapest 1085, Hungary., Schvarcz CA; Institute of Translational Medicine, Semmelweis University, Üllői út 26., Budapest 1085, Hungary.; HUN-REN-SU Cerebrovascular and Neurocognitive Diseases Research Group, Tűzoltó utca 37-47., Budapest 1094, Hungary., Bócsi D; Institute of Translational Medicine, Semmelweis University, Üllői út 26., Budapest 1085, Hungary., Koós Z; Institute of Translational Medicine, Semmelweis University, Üllői út 26., Budapest 1085, Hungary., Benyó Z; Institute of Translational Medicine, Semmelweis University, Üllői út 26., Budapest 1085, Hungary.; HUN-REN-SU Cerebrovascular and Neurocognitive Diseases Research Group, Tűzoltó utca 37-47., Budapest 1094, Hungary., Hamar P; Institute of Translational Medicine, Semmelweis University, Üllői út 26., Budapest 1085, Hungary.
Jazyk:	angličtina
Zdroj:	ACS pharmacology & translational science [ACS Pharmacol Transl Sci] 2024 Jul 17; Vol. 7 (8), pp. 2496-2506. Date of Electronic Publication: 2024 Jul 17 (Print Publication: 2024).
DOI:	10.1021/acsptsci.4c00314
Abstrakt:	Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype, with limited treatment options. Modulated electro-hyperthermia (mEHT) is a novel adjuvant cancer therapy that induces selective cancer damage. However, mEHT upregulates heat shock protein beta 1 (HSPB1), a cancer-promoting stress chaperone molecule. Thus, we investigated whether ivermectin (IVM), an anthelmintic drug, may synergize with mEHT and enhance its anticancer effects by inhibiting HSPB1 phosphorylation. Isogenic 4T1 TNBC cells were inoculated into BALB/c mice and treated with mEHT, IVM, or a combination of both. IVM synergistically improved the tumor growth inhibition achieved by mEHT. Moreover, IVM downregulated mEHT-induced HSPB1 phosphorylation. Thus, the strongest cancer tissue damage was observed in the mEHT + IVM-treated tumors, coupled with the strongest apoptosis induction and proliferation inhibition. In addition, there was no significant body weight loss in mice treated with mEHT and IVM, indicating that this combination was well-tolerated. In conclusion, mEHT combined with IVM is a new, effective, and safe option for the treatment of TNBC. Competing Interests: The authors declare no competing financial interest. (© 2024 The Authors. Published by American Chemical Society.)
Databáze:	MEDLINE
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