Intratumoral Treatment with 5-Androstene-3β, 17α-Diol Reduces Tumor Size and Lung Metastasis in a Triple-Negative Experimental Model of Breast Cancer

• Published in: International journal of molecular sciences Vol. 23; no. 19; p. 11944
• Main Authors: Ruiz Manzano, Rocío Alejandra, Nava-Castro, Karen Elizabeth, Palacios-Arreola, Margarita Isabel, Hernández-Cervantes, Rosalía, Del Río-Araiza, Víctor Hugo, Segovia-Mendoza, Mariana, Pérez-Torres, Armando, Girón-Pérez, Manuel Iván, Morales-Montor, Jorge
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 08-10-2022; MDPI
• Subjects: alpha-androstenediol; Antiproliferatives; Biocompatibility; Breast cancer; breast tumor; Cancer therapies; Cell growth; Cell proliferation; Drug delivery; Estrogens; Immune system; Immunoglobulin G; In vivo methods and tests; intratumoral treatment; Lung cancer; Lungs; Mammary gland; Metastases; Metastasis; Natural killer cells; Steroids; translational medicine; Tumor cells; tumor microenvironment; Tumors; Vascular endothelial growth factor
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms231911944

Breast cancer treatment failure is related to low response rates, high costs, and long-term toxicities. Thus, it is necessary to find less toxic, cheaper, and more effective treatments. In situ administration ensures drug delivery to tumor cells and decreases systemic toxic effects. The androstene-3β, 17α-diol (α-AED) reduces breast tumor cell proliferation and is an ideal candidate to treat mammary tumors. This study aims to identify the in vitro and in vivo effects of α-AED on a triple-negative mammary tumor model. An in vitro biphasic steroid effect was observed in mouse and human mammary tumor cells treated with α-AED. In this sense, cells treated with higher doses (100 and 200 μM) showed an antiproliferative effect. The α-AED administrated intratumorally reduced average tumor weight and increased the percentage of natural killer cells (NK), plasmatic, and plasmablast cells in mice tumors. Of note, VEGF levels in all α-AED-treated tumors was lower than in the control and vehicle groups. The tumor in situ increased response was reflected systemically by higher anti-4T1 IgG concentration in serum from α-AED-treated mice, but no other associated systemic changes were detected. The reduction in tumor size for the local injection of α-AED is associated with the anti-proliferative effect of this steroid, and the lower local levels of VEGF may be related to the imperceptible macroscopic metastasis in α-AED-treated mice. The above suggests that α-AED may be used in clinical studies to prove its efficacy as an alternative breast tumor treatment or in conjunction with already established therapies.