145391 20260217205531.0 doi 10.1186/s12967-024-05739-x sideral 140296 ART-2024-140296 eng Soler-Agesta, R. Universidad de Zaragoza Cancer cell-selective induction of mitochondrial stress and immunogenic cell death by PT-112 in human prostate cell lines 2024 Access copy available to the general public Unrestricted PT-112 is a novel immunogenic cell death (ICD)-inducing small molecule currently under Phase 2 clinical development, including in metastatic castration-resistant prostate cancer (mCRPC), an immunologically cold and heterogeneous disease state in need of novel therapeutic approaches. PT-112 has been shown to cause ribosome biogenesis inhibition and organelle stress followed by ICD in cancer cells, culminating in anticancer immunity. In addition, clinical evidence of PT-112-driven immune effects has been observed in patient immunoprofiling. Given the unmet need for immune-based therapies in prostate cancer, along with a Phase I study (NCT#02266745) showing PT-112 activity in mCRPC patients, we investigated PT-112 effects in a panel of human prostate cancer cell lines. PT-112 demonstrated cancer cell selectivity, inhibiting cell growth and leading to cell death in prostate cancer cells without affecting the non-tumorigenic epithelial prostate cell line RWPE-1 at the concentrations tested. PT-112 also caused caspase-3 activation, as well as stress features in mitochondria including ROS generation, compromised membrane integrity, altered respiration, and morphological changes. Moreover, PT-112 induced damage-associated molecular pattern (DAMP) release, the first demonstration of ICD in human cancer cell lines, in addition to autophagy initiation across the panel. Taken together, PT-112 caused selective stress, growth inhibition and death in human prostate cancer cell lines. Our data provide additional insight into mitochondrial stress and ICD in response to PT-112. PT-112 anticancer immunogenicity could have clinical applications and is currently under investigation in a Phase 2 mCRPC study. info:eu-repo/grantAgreement/ES/MICINN/PID2019-105128RB-I00 info:eu-repo/semantics/openAccess by-nc-nd https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es 7.5 2024 MEDICINE, RESEARCH & EXPERIMENTAL 24 / 195 = 0.123 2024 Q1 T1 1.997 2024 Medicine (miscellaneous) 2024 Q1 Biochemistry, Genetics and Molecular Biology (miscellaneous) 2024 Q1 8.8 2024 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Moreno-Loshuertos, R. Universidad de Zaragoza (orcid)0000-0002-6600-1618 Yim, C. Y. Congenie, M. T. Ames, T. D. Johnson, H. L. Stossi, F. Mancini, M. G. Mancini, M. A. Ripollés-Yuba, C. Universidad de Zaragoza Marco-Brualla, J. Junquera, C. Universidad de Zaragoza (orcid)0000-0002-9951-1075 Martínez-De-Mena, R. Enríquez, J. A. Price, M. R. Jimeno, J. Anel, A. Universidad de Zaragoza (orcid)0000-0002-5175-8394 1003 443 Universidad de Zaragoza Dpto. Anatom.Histolog.Humanas Area Histología 1002 060 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Bioquímica y Biolog.Mole. 22, 1 (2024), 927 [17 pp.] J. transl. med. Journal of translational medicine 1479-5876 9875681 http://zaguan.unizar.es/record/145391/files/texto_completo.pdf Versión publicada 2117346 http://zaguan.unizar.es/record/145391/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:145391 articulos driver 2026-02-17-20:32:42 ARTICLE