Norcantharidin and Levoglucosenone: new natural alternatives for breast cancer treatment

Lizeth Aixa Ariza Bareño, Damián Delbart, Andrés Bechis, Natalia Amigo, María Agustina Taruselli, Laura B. Todaro, Alejandro J. Urtreger

In this work we have studied the antitumor activity of two different natural compounds: Norcantharidin (NCTD) and levoglucosenone (Levo). NCTD is a demethylated form of cantharidin, an active component present in Mylabris beetles and Levo is obtained after the pyrolytic treatment of soybean hulls. NCTD showed an IC50 of 35 and 56 μM in 4T1 and Hs578T mammary cell lines respectively.
Levo and structurally related derivatives (compounds 2, 3 and 4) were analyzed in LM3 and MDA-MB 231 cell lines showing an IC50 of 12 and 50 μM respectively.
Anti-proliferative effects were associated with apoptosis induction. Besides, NCTD also induced a time-sustained reduction in p-ERK levels. In vitro, both compounds
significantly reduced the adhesive and migratory capacities as well as secreted MMP-9 activity in a dose-dependent manner (p<0.05 Anova). Although these parameters could have a direct implication in malignant progression, in vivo assays pretreating 4T1 cells with NCTD, showed an 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 observed after employing Levo.
In sum, all the compounds analyzed show promising effects against breast cancer and may become in the future an important therapeutic alternatives.