Abstract
<div>Abstract<p>We report the discovery, via a unique high-throughput screening strategy, of a novel bioactive anticancer compound: <u>T</u>hiol <u>A</u>lkylating <u>C</u>ompound <u>I</u>nducing <u>M</u>assive <u>A</u>poptosis (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.</p></div>
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