TACIMA-218: A Novel Pro-Oxidant Agent Exhibiting Selective Antitumoral Activity
In: Molecular Cancer Therapeutics, Jg. 20 (2021), S. 37-49
Online
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Zugriff:
We report the discovery, via a unique high-throughput screening strategy, of a novel bioactive anticancer compound: Thiol Alkylating Compound Inducing Massive Apoptosis (TACIMA)-218. We demonstrate that this molecule engenders apoptotic cell death in genetically diverse murine and human cancer cell lines, irrespective of their p53 status, while sparing normal cells. TACIMA-218 causes oxidative stress in the absence of protective antioxidants normally induced by Nuclear factor erythroid 2–related factor 2 activation. As such, TACIMA-218 represses RNA translation and triggers cell signaling cascade alterations in AKT, p38, and JNK pathways. In addition, TACIMA-218 manifests thiol-alkylating properties resulting in the disruption of redox homeostasis along with key metabolic pathways. When administered to immunocompetent animals as a monotherapy, TACIMA-218 has no apparent toxicity and induces complete regression of pre-established lymphoma and melanoma tumors. In sum, TACIMA-218 is a potent oxidative stress inducer capable of selective cancer cell targeting.
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TACIMA-218: A Novel Pro-Oxidant Agent Exhibiting Selective Antitumoral Activity
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Autor/in / Beteiligte Person: | Mercier, Francois ; Noël J.-M. Raynal ; Annabi, Borhane ; Cui, Yun ; Pelletier, Jerry ; Wurtele, Hugo ; Robert, Francis ; Abusarah, Jamilah ; El-Hachem, Nehme ; Beaudry, Annie ; Jankovic, Maja ; Abed El-Hakim El-Kadiry ; Rafei, Moutih ; Kamyabiazar, Samaneh ; Hammond-Martel, Ian |
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Zeitschrift: | Molecular Cancer Therapeutics, Jg. 20 (2021), S. 37-49 |
Veröffentlichung: | American Association for Cancer Research (AACR), 2021 |
Medientyp: | unknown |
ISSN: | 1538-8514 (print) ; 1535-7163 (print) |
DOI: | 10.1158/1535-7163.mct-20-0333 |
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