en Cell Biology Cell Biology Original Article Original Article <a name="_Hlk13344521">Zinc as therapeutic agent in skin and wound care has been known for centuries, but its role is controversial and comprehensive investigations in nutrient-deficient environments are lacking. </a>We aimed to provide a broad analysis of different zinc derivatives on proliferation, apoptosis and antimicrobial properties in a simulated nutrient-deficient environment <em>in vitro</em>. Human fibroblasts (CRL2522) and keratinocytes (HaCaT) were treated with a broad concentration range (10 &ndash; 0.0001 &micro;g/mL) of zinc-sulfate (ZnSO₄), -gluconate (ZnGluc) and -histidine (ZnHis) for 1-6 days under nutrient-deficient media conditions. Cell proliferation was investigated by XTT assay. Targeted analyzes in proliferation (<em>E2F1</em>, <em>PCNA</em>) and apoptosis (<em>TP53</em>) associated genes were performed via qRT-PCR and apoptosis was determined via FACS (annexin V/7-AAD staining). Antimicrobial efficacy was investigated using a quantitative suspension method against <em>S. aureus</em>, <em>P. aeruginosa</em>, <em>E. coli</em>, and <em>C. albicans</em>. The results indicated that 0.1 to 0.001 &micro;g/mL Zn increased cell proliferation in both cell lines. Fibroblasts were more susceptible with significant proliferation peaks on days 2 & 6, and days 1 & 4 for keratinocytes. No relevant changes in gene expression were detected for <em>E2F1</em> and <em>PCNA</em> nor for <em>TP53</em>. Annexin-V/7-AAD-staining of fibroblasts revealed a small, yet insignificant reduction of apoptosis induction for ZnGluc and ZnSO₄. ZnGluc and ZnSO₄(0.1%) achieved high microbial reductions (4-5 log₁₀ reductions) against tested pathogens. ZnGluc and ZnSO₄ showed relevant pro-proliferative and antimicrobial, as well as tendential anti-apoptotic features in a simulated nutrient-deficient microenvironment <em>in vitro</em>. This further validates a potential benefit of local zinc treatment in deficient wound microenvironments. Wound healing, zinc, fibroblasts, keratinocytes, antimicrobial efficacy, cell proliferation, apoptosis 165 179 http://ijmcmed.org/browse.php?a_code=A-10-2522-1&slc_lang=en&sid=1 Julian-Dario Rembe julian-dario.rembe@uni-wh.de 100319475328460019010 100319475328460019010 Yes Department of Vascular and Endovascular Surgery, Heinrich-Heine-University, Düsseldorf, Germany. Julia Katharina Boehm julia.boehm@uni-wh.de 100319475328460019011 100319475328460019011 No Institute for Research in Operative Medicine (IFOM), Witten/Herdecke University. Carolin Fromm-Dornieden carolinfromm@gmx.de 100319475328460019012 100319475328460019012 No Institute for Research in Operative Medicine (IFOM), Witten/Herdecke University. Nina Hauer nina.hauer@uni-wh.de 100319475328460019013 100319475328460019013 No Chair for Translational Wound Research, Centre for Biomedical Education and Research (ZBAF), Witten/Herdecke University. Ewa Klara Stuermer e.stuermer@uke.de 100319475328460019014 100319475328460019014 No Department of Vascular Medicine, University Heart Center, Translational Wound Research, University Medical Center Hamburg-Eppendorf.