MCW Researchers Publish Article on the Potential Antitumor Immunomodulatory Mechanism of Mito-HU
Hydroxyurea (HU), which is FDA-approved to treat sickle cell disease, is used as an antitumor drug alone and together with conventional chemotherapeutics or radiation therapy to treat myeloproliferative diseases. The hydroxyl group in HU is considered critical for its antiproliferative and chemotherapeutic effects. MCW researchers substituted the hydroxyl group in HU with a triphenylphosphonium cation attached to an alkyl group with different chain lengths, forming a new class of mitochondria-targeted HU (Mito-HU).
In a recently published iScience article, “Mitochondria-targeted hydroxyurea inhibits OXPHOS and induces antiproliferative and immunomodulatory effects,” MCW researchers discuss how Mito-HU targets oxidative phosphorylation and inhibits cancer cell proliferation at sub-micromolar levels. The antiproliferative potency increased with the increasing hydrophobicity of the Mito-HUs. Additionally, Mito-HUs may inhibit myeloid-derived suppressor cells and neutrophils as well as activate T cells, implicating their potential antitumor immunomodulatory mechanism.
The corresponding author of the article is Balaraman Kalyanaraman, PhD, professor and chair of biophysics and the Harry R. & Angeline E. Quadracci Professor in Parkinson’s Research. Other collaborating authors include Gang Cheng, PhD, research scientist II in biophysics; Micael Hardy, PhD, Aix-Marseille Universite, France; Paytsar Topchyan, MS, MSTP graduate student in microbiology & immunology; Ryan Zander, PhD, postdoctoral fellow at Versiti Blood Research Institute; Peter Volberding, PhD, formerly a postdoctoral fellow at Versiti Blood Research Institute; Weiguo Cui, MD, PhD, associate professor of microbiology & immunology, and investigator at Versiti Blood Research Institute.