The Extra Virgin Olive Oil phenolic compounds () oleacein and () oleocanthal inhibit tumor cell autophagy

Es una comunicación a congreso internacional en formato póster.Our group has recently shown that the antitumor Extra Virgin Olive Oil phenolic compounds (—)oleocanthal and (—)oleacein also behave as antiangiogenic agents. Interestingly, it has been described that phenolic compounds found in the Mediterranean diet affect the autophagy pathway. Based on this background, we studied the modulatory effects of (—)oleocanthal and (—)oleacein on tumor cell autophagy. Methodologically, the tumor cell lines MDAMB231, MCF7 and HT1080 cell lines were used in in vitro cellular and molecular studies of the autophagy flux and key mediators of this process, and High Content Screening (HCS) System using Perkin Elmer Operetta for single-cell analysis was performed in these cells. Interestingly, (—)oleocanthal and (—)oleacein repressed the autophagy flux of MDAMB231 and MCF7 submitted to autophagy inducing conditions (severe starving) at doses in the low micromolar range. In addition, key autophagy mediators, like LC3 or WIPI2 proteins, were dramatically reduced in the same settings, as seen in immunohistochemical studies. Furthermore, preliminary results of HCS in tumor cells revealed depletory effects on autophagy by using specifics dyes for this process at the single-cell level. Altogether, our results point to a drastic inhibitory effect of (—)oleocanthal and (—)oleacein on tumor cell autophagy at low doses.[Grants: PID2022-138181OB-I00, PID2019-105010RB-I00 and RTI2018-098560-BC22 (Spanish Government), UMA18-FEDERJA-220, and PY20_00257 (Andalusian Government and FEDER). Funds from BIO 267 (Andalusian Government) M.B. is supported by “Juan de la Cierva – Incorporation Program” (IJC2018-037657-I), Spanish Ministry of Science and Innovation, Spain.]. Supported with a a help from the «II Plan Propio de Investigación, Transferencia y Divulgación Científica de la UMA», Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

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