URTREGER Alejandro Jorge
congresos y reuniones científicas
Study of antitumoral activity of compounds derived from natural products. effect of naphtoquinones on breast cancer progression
LUCIANA CAÑONERO; ALDANA SCHEY; LIZETH ARIZA BAREÑO; ANDRES BECHIS; DIEGO BRITEZ NEIRA; JULIÁN FERNANDEZ; JUAN ROBIROSA; JORGE PALERMO; LAURA B. TODARO; ALEJANDRO J. URTREGER
Mar del Plata
Congreso; LXVII Reunión Científica de la Sociedad Argentina de Investigación Clínica (SAIC); 2022
Sociedad Argentina de Investigación Clínica (SAIC)
Breast cancer is a major public health problem, being the second leading cause of cancer death in women on developed countries. Conventional therapies such as surgery, chemotherapy and radiotherapy seem to have reached a plateau of therapeutic efficacy. Therefore, the study of naphthoquinones, a family of natural compounds (and semi-synthetic derived compounds) is proposed as an alternative for the treatment of these neoplasms. Naphthoquinones are a group of highly reactive organic species that present anti-inflammatory activities at very low toxicity rates and till nowadays their usefulness in oncology remains unexplored.In the present work, eleven 5-(N-indolyl)-1,4-naphthoquinones substituted with anilines at C-2 or C-3 were tested, employing normal and tumor derived mammary cell lines. The original naphthoquinone (N0) and 3 derivatives (named 4-pMT, 5-AnT and 6-AnC) showed a strong antiproliferative effect with an Inhibitory Concentrations 50 (IC50) of 5.8±0.2 µM, 15.25±2.5 µM, 24.7±1.9 µM and 9.9±1.2 µM respectively (MTS assays). Through flow cytometry we could determine that LM3 cells, treated with the N0 and 5-AnT compounds, increased the Sub-G0 and S fractions of the cell cycle, events compatible with the presence of apoptotic cells and with an impairment in cell replication respectively. These compounds also increased the expression BAX and PARP two proapoptotic markers, analyzed by Western Blot. In contrast, in the normal cell line NMuMG, no significant alterations were observed in cell cycle stages or in the aforementioned apoptotic markers. Based on these results, we consider that naphthoquinones and their derivatives are promising compounds to continue their study in preclinical settings and may, in the future, become a new tool for the treatment of breast cancer.