Romanian Society of Pharmaceutical Sciences
 

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GALLIC ACID-ZINC(II) METALLOCOMPLEX EXERTS A STRONGER CYTOTOXICITY THAN GALLIC ACID IN U2OS CELLS

IONUȚ IULIAN LUNGU 1#, BOGDAN HUZUM 2#, ȘTEFANIA-IRINA DUMITREL 3,4#, SILVIU BRAD 5*, OANA CIOANCĂ 1, CORNELIA MIRCEA 1, CRISTINA ADRIANA DEHELEAN 6, MONICA HĂNCIANU ¹

¹ Faculty of Pharmacy, “Grigore T. Popa” University of Medicine and Pharmacy of Iași, 16 Universității Street, 700115, Iași, Romania
2 Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy of Iași, 700115, Iași, Romania
3 Research Center for Pharmaco-Toxicological Evaluations, “Victor Babeș” University of Medicine and Pharmacy Timișoara, 2 Eftimie Murgu Square, 300041, Timișoara, Romania
4 Department of Toxicology, Drug Industry, Management and Legislation, Faculty of Pharmacy, “Victor Babeș” University of Medicine and Pharmacy Timișoara, 2 Eftimie Murgu Square, 300041, Timișoara, Romania
5 Department of Radiology and General & Dento-Maxillofacial Medical Imaging, Faculty of Dental Medicine, “Victor Babeș” University of Medicine and Pharmacy Timișoara, 2 Eftimie Murgu Square, 300041 Timișoara, Romania
6 Research Center for Pharmaco-Toxicological Evaluations, Faculty of Pharmacy, “Victor Babeș” University of Medicine and Pharmacy Timișoara, 2 Eftimie Murgu Square, 300041, Timișoara, Romania

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Osteosarcoma (OS) is the most frequent type of bone cancer. Due to resistance to treatment and the toxic reactions linked with conventional therapy, other alternatives are being researched. Gallic acid (GA) has emerged as a promising candidate for the treatment of bone diseases and OS, as it has been shown to induce osteogenic differentiation, promote bone regeneration, repress osteoclastogenesis, protect preosteoblasts against external injury, and induce tumor cell death. One of the most emergent directions in chemotherapy development is the metal chelation of bioactive molecules, a strategy that generates complexes with improved therapeutic properties, enhanced selectivity, and minimized toxicity. For these reasons, the present study was designed to comparatively investigate the cytotoxic activity of GA and GA-Zn(II) against U2OS cells. The results demonstrated that Zn(II) complexation potentiated the antitumor activity of gallic acid, as evidenced by enhanced cytotoxicity in U2OS cells, reduced clonogenic potential, and pronounced apoptotic morphological alterations, while showing lower cytotoxicity in the VERO cell line and maintaining a non-irritant profile.