Oral squamous cell carcinoma is considered one of the most prevalent subtypes of head and neck cancers. Treatments include surgical resection, radiotherapy, and chemotherapy in the cases of patients with advanced squamous cell carcinoma (SCC). Cisplatin, or cis-diamminedichloridoplatinum(II), has been used for treatment of several types of cancer worldwide since 1978 including advanced head and neck SCC. The successful use of cisplatin led to the development of second-generation platinum-based drugs, with emphasis on carboplatin and oxaliplatin, which have been used for cancer treatment worldwide. Nevertheless, patients treated with platinum drugs as cisplatin are subjected to adverse effects as nephrotoxicity, and the search for new chemotherapeutic agents with reduced side effects is crucial. After the discovery of the platinum anticancer drugs, new metal-based compounds of copper, silver, gold, ruthenium, palladium and iridium were synthesized and evaluated as potential anticancer agents. Padeliporfin (Tookad®Soluble) was the first palladium(II) complex used in vascular targeted photochemotherapy for low-risk prostate cancer treatment, which also confirms the potential of use of this metal in the synthesis of new chemotherapeutic agents. In this context, our research group has dedicated efforts in the search of novel gold, silver, platinum and palladium complexes for treatment of cancer, with emphasis on SCC. One of the silver complexes with the anti-inflammatory drug nimesulide recently prepared in our group demonstrated in vitro and in vivo activity over SCC cells.

This study aimed to present the in vitro anti-proliferative activities over SCC of a water-soluble palladium(II) complex containing a cysteine derivative as a chelating ligand.

SCC of tongue (SCC4 and SCC15) and a non-tumoral cell line (HaCat, immortalized keratinocyte) were used in this study. The cells were cultivated following methodology previously described in the literature.

The palladium(II) complex inhibited proliferation of SCC15 cells with a GI50 (concentration of a drug that reduces cell growth by 50%) of 40.28 µg mL 1 but low selectivity was observed when compared to HaCat cells (GI50: 28.33 µg mL 1). On the other hand, the complex did not inhibit SCC4 cell proliferation (GI50 > 250 µg mL 1).

The palladium(II) complex seems to be indicated for treatment of SCC of tongue, but further studies are envisaged to understand the selectivity of the complex over the considered SCC lines and propose its possible mechanism of action.

This study was supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq #309800/2021-8; #429463/2018-9), Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) for the Cancer Theranostics Innovation Center (CancerThera), CEPID FAPESP #2021/10265-8), and International Atomic Energy Agency (IAEA) technical cooperation projects for development of Latin American Countries (IAEA/TCLAC: EX-BRA6033-2401375).