URTREGER Alejandro Jorge
congresos y reuniones científicas
Norcantharidin and levoglucosenone: new natural alternatives for breast cancer treatment
LIZETH ARIZA BAREÑO; DAMIAN DELBART; ANDRES BECHIS; NATALIA AMIGO; LUCIANA CAÑONERO; LAURA B. TODARO; ALEJANDRO J. URTREGER
Congreso; LXV Reunión Científica de la Sociedad Argentina de Investigación Clínica (SAIC); 2020
Sociedad Argentina de Investigación Clínica (SAIC)
Breast cancer is a major public health problem, being the second leading cause of cancer death among women in developed countries. Given the need for new therapeutic alternatives, in this work we have studied the antitumor activity of two different natural compounds in order to evaluate their potential use in clinical settings. Norcantharidin (NCTD) is a demethylated form of cantharidin, an active component present in Mylabris beetles and levoglucosenone (Levo) is obtained after the pyrolytic treatment of soybean hulls. NCTD showed an IC50 of 35 and 56 uM in 4T1 (murine) and Hs578T (human) mammary cell lines respectively. Levo and structurally related derivatives (compounds 2, 3 and 4) were analyzed in LM3 (murine) and MCF 7 (human) cell lines showing an IC50 of 12 and 50 uM respectively. In both natural compounds, anti-proliferative effects were associated with apoptosis induction. Nevertheless, NCTD also induced a time-sustained reduction in ERK activated levels (p-ERK). Moreover, in vitro, both compounds significantly reduced the adhesive and migratory capacities as well as secreted MMP-9 activity in a dose-dependent manner.Although these parameters could have a direct implication in malignant progression, in vivo assays pretreating 4T1 cells with NCTD, showed a significant increase in experimental metastatic spread. However, applying the same experimental approach, Levo and compound 2 significantly reduced the number of LM3 lung nodules. Furthermore, systemic treatment of BALB/c mice induced a significant inhibition of tumor growth upon using compound 2 and a partial effect was obtained after employing Levo. In sum, all the compounds analyzed show promising effects against breast cancer and may become in the future an important therapeutic alternative, either as a single drug or enhancing the effect of pre-existing therapies.