Antineoplastic activity of products derived from cellulose-containing materials: levoglucosenone and structurally-related derivatives as new alternatives for breast cancer treatment

DELBART, DAMIAN IGNACIO; GIRI, GERMAN FRANCISCO; CAMMARATA, AGOSTINA; BAREÑO, LIZETH ARIZA; AMIGO, NATALIA LORELEY; BECHIS, ANDRÉS; SUAREZ, ALEJANDRA GRACIELA; SPANEVELLO, ROLANDO ÁNGEL; TODARO, LAURA BEATRIZ; URTREGER, ALEJANDRO JORGE

INVESTIGATIONAL NEW DRUGS

SPRINGER

Lugar: Berlin; Año: 2021

0167-6997

SummaryBreast cancer is the leading cause of cancer death among women worldwide. For this reason, the development of newtherapies is still essential. In this work we have analyzed the antitumor potential of levoglucosenone, a chiral building blockderived from the pyrolysis of cellulose-containing materials such as soybean hulls, and three structurally related analogues.Employing human and murine mammary cancer models, we have evaluated the effect of our compounds on cell viabilitythrough MTS assay, apoptosis induction by acridine orange/ethidium bromide staining and/or flow cytometry and the lossof mitochondrial potential by tetramethylrhodamine methyl ester staining. Autophagy and senescence induction were alsoevaluated by Western blot and β-galactosidase activity respectively. Secreted metalloproteases activity was determined byquantitative zymography. Migratory capacity was assessed by wound healing assays while invasive potential was analyzedusing Matrigel-coated transwell chambers. In vivo studies were also performed to evaluate subcutaneous tumor growth andexperimental lung colonization. All compounds impaired in vitro proliferation with IC50values in a range of low micromolar.Apoptosis was identified as the main mechanism responsible for the reduction of monolayer cell content induced by thecompounds without detecting modulations of autophagy or senescence processes. Two of the four compounds (levoglucosenoneand its brominated variant) were able to modulate in vitro events associated with tumor progression, such as migratorypotential, invasiveness, and proteases secretion. Furthermore, tumor volume and metastatic spread were significantly reducedin vivo after the treatment these two compounds. Here, we could obtain from soybean hulls, a material with almost no commercialvalue, a variety of chemical compounds useful for breast cancer treatment.