Pd(2)Spermine Complex Shows Cancer Selectivity and Efficacy to Inhibit Growth of Triple-Negative Breast Tumors in Mice

• Type: Article in International Scientific Journal
• Date: 2022

Authors

Vojtek, M (Author) Other; Goncalves Monteiro, S (Author) Other; Seminska, P (Author) Other; Valova, K (Author) Other; Bellon, L (Author) Other; Dias Pereira, P (Author) Other; Marques, F (Author) Other; Marques, MPM (Author) Other; de Carvalho, ALMB (Author) Other; Mota Filipe, H (Author) Other; Ferreira, IMPLVO (Author) Other; Diniz, C (Author) FFUP

Journal

Title: Biomedicines

Vol. 136

Final page: 210

Publisher: MDPI

Indexing

ISI Web of Knowledge - 0 Citations

Scopus - 0 Citations

Other information

Authenticus ID: P-00W-0VX

DOI: 10.3390/biomedicines10020210

Abstract (EN): Pd(2)Spm is a dinuclear palladium(II)-spermine chelate with promising anticancer properties against triple-negative breast cancer (TNBC), a breast carcinoma subset with poor prognosis and limited treatment options. The present study evaluated the in vitro and in vivo anticancer effects of Pd(2)Spm compared to the reference metal-based drug cisplatin. Triple-negative breast cancer MDA-MB-231 cells, non-cancerous MCF-12A breast cells and chorioallantoic membrane (CAM) assay were used for antiproliferative, antimigratory and antiangiogenic studies. For an in vivo efficacy study, female CBA nude mice with subcutaneously implanted MDA-MB-231 breast tumors were treated with Pd(2)Spm (5 mg/kg/day) or cisplatin (2 mg/kg/day) administered intraperitoneally during 5 consecutive days. Promising selective antiproliferative activity of Pd(2)Spm was observed in MDA-MB-231 cells (IC50 values of 7.3-8.3 mu M), with at least 10-fold lower activity in MCF-12A cells (IC50 values of 89.5-228.9 mu M). Pd(2)Spm inhibited the migration of MDA-MB-231 cells, suppressed angiogenesis in CAM and decreased VEGF secretion from MDA-MB-231 cells with similar potency as cisplatin. Pd(2)Spm-treated mice showed a significant reduction in tumor growth progression, and tumors evidenced a reduction in the Ki-67 proliferation index and number of mitotic figures, as well as increased DNA damage, similar to cisplatin-treated animals. Encouragingly, systemic toxicity (hematotoxicity and weight loss) observed in cisplatin-treated animals was not observed in Pd(2)Spm-treated mice. The present study reports, for the first time, promising cancer selectivity, in vivo antitumor activity towards TNBC and a low systemic toxicity of Pd(2)Spm. Thus, this agent may be viewed as a promising Pd(II) drug candidate for the treatment of this type of low-prognosis neoplasia.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 20