The synthetic molecule stauprimide impairs cell growth and migration in triple-negative breast cancer

Stauprimide, a semi-synthetic derivative of staurosporine, is known mainly for its potent differentiation-enhancing properties in embryonic stem cells. Here, we studied the effects of stauprimide in cell growth and migration of triple-negative breast cancer cells in vitro, evaluating its potential antitumoral activity in an orthotopic mouse model of breast cancer in vivo. Our results from survival curves, EdU incorporation, cell cycle analysis and annexin-V detection in MDA-MB-231 cells indicated that stauprimide inhibited cell proliferation, arresting cell cycle in G2/M without induction of apoptosis. A decrease in the migratory capability of MDA-MB-231 was also assessed in response to stauprimide. In this work we pointed to a mechanism of action of stauprimide involving the modulation of ERK1/2, Akt and p38 MAPK signalling pathways, and the downregulation of MYC in MDA-MB-231 cells. In addition, orthotopic MDA-MB-231 xenograft and 4T1 syngeneic models suggested an effect of stauprimide in vivo, increasing the necrotic core of tumors and reducing metastasis in lung and liver of mice. Together, our results point to the promising role of stauprimide as a putative therapeutic agent in triple-negative breast cancer.MRI experiments were performed in the ICTS “NANBIOSIS”, more specifically in the U28 Unit at the Andalusian Centre for Nanomedicine & Biotechnology (BIONAND). Cell cultures were performed in the Cell Culture Service at the Central Support Services of Research (SCAI) of the University of Málaga. // Partial funding for open access charge: Universidad de Málaga / CBUA

Study of the antitumor potential of stauprimide in breast cancer

Contribución a Congreso (póster)Stauprimide, a semi-synthetic derivative of staurosporine, was characterized in 2009 as a potent differentiation-enhancing compound in embryonic stem cells [1]. Although it was first thought that this compound could maintain the properties of staurosporine as a non-selective inhibitor of protein kinases (especially potent in inhibiting tyrosine kinases), it was found that its potential as an inhibitor of these proteins was not particularly remarkable, ruling out this as its main mechanism of action for the differentiation-enhancing effect. However, a clear effect of stauprimide on embryonic stem cells was identified as an inhibitor of CMYC expression, a key factor in the maintenance of stem cell pluripotency [1]. Given the involvement of CMYC in cancer development, and the effect of stauprimide inhibiting its expression, this compound was proposed as a possible antitumor drug in the treatment of renal cancer [2]. In this work we have studied the in vitro antitumor effect of stauprimide in the context of breast cancer, exploring also the possible mechanisms of action by which stauprimide exerts its effects. The detected activity of this compound on the human adenocarcinoma model used in our studies suggests its potential usefulness in antitumor pharmacological strategies.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. Este trabajo está financiado por fondos de los proyectos PID2019-105010RB-100 (Ministerio de Ciencia, Gobierno de España), UMA18-FEDERJA-220 (Junta de Andalucía y fondos FEDER), Ayudas a Proyectos de Investigación en Salud del Plan Propio de IBIMA 2020 y fondos del grupo BIO-267 (Junta de Andalucía)