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Cancer is one of the leading causes of morbidity and mortality worldwide. This disease is characterized by uncontrolled growth and proliferation of abnormal cells with a high probability to develop metastasis. Recently, it was demonstrated that perezone, a sesquiterpene quinone, is capable to induce cell death in leukemia (K562), prostate (PC-3), colorectal (HCT-15) and lung (SKLU-1) cancer cell lines; however, its mechanism of action is unknown. Therefore, in this study, in vitro and computational studies were performed to determine the mechanism of action of perezone. Firstly, changes in K562 cell viability, as well as changes in the redox status of the cell in response to treatment with several concentrations of perezone were analyzed. The type of cell death induced, and the modification of the cell cycle were determined. In addition, MD simulations and docking studies were performed to investigate the interaction of perezone with seven regulators of the apoptotic process. Finally, the ability of perezone to inhibit PARP-1 was evaluated by in vitro studies. K562 cells treated with perezone exhibited decreased viability and more oxidized status, being this effect concentration-dependent. In addition, the increase of G0/G1 phase of cell cycle and apoptosis were observed. According to the performed computational studies conducted, perezone showed the highest affinity to PARP-1 enzyme being this complex the most stable due to the presence of a small and deep cavity in the active site, which allows perezone to fit deeply by forming hydrogen bonds and hydrophobic interactions, which drive this interaction. The activity of perezone as PARP-1 inhibitor was corroborated with an IC 50 = 181.5 μM. The pro-apoptotic action of perezone may be related to PARP-1 inhibition and changes in the redox state of the cell. The obtained results allowed to understand the biological effect of perezone and, consequently, these could be employed to develop novel PARP-1 inhibitors. Image 1 • Perezone induces cell death in cancer cell lines. • K562 cells treated with perezone exhibited decreased viability and more oxidized status. • K562 cells treated with perezone increase in G0/G1 cell cycle and apoptosis. • In addition, perezone was confirmed as PARP-1 inhibitor by computational and in vitro evaluation. • The pro-apoptotic action of perezone may be related to changes in the redox state of the cell and PARP-1 inhibition. [ABSTRACT FROM AUTHOR]

The gelation and melting temperatures of calcium-induced κ-carrageenan gels in the range of ionic strength 0–40 mmol/L were measured by small deformation oscillatory rheology. Theoretical studies of the interactions between dimeric unit models that form the κ-carrageenan polymer chain with Ca2+ cations were also carried out by means of quantum chemistry techniques using density functional theory with M06-2X/6-311G**. Gelling (on cooling) and melting (on heating) temperatures moved to progressively higher temperatures upon the progressive addition of CaCl 2 , yielding thermal hysteresis. The interactions of the κ-carrageenan model with Ca2+ ions were analyzed, and the results showed that κ-carrageenan can exhibit intra- and intermolecular hydrogen bonding and coordination with Ca2+ ions. The interaction energies that can present conformers of the κ-carrageenan model were located between 25.1 and 46.02 kJ/mol. Coordination between the Ca2+ cation and the polymer as well as the intra- and intermolecular interactions of two sugars may be one of the factors by which Ca2+ ions could promote the coil-helix transition, resulting in the formation of more aggregates acting as junction zones. • The gelling and melting temperatures of the κ-carrageenan–Ca2+ system were determined by the tan δ method. • The sol-gel transition diagram of κ-carrageenan in the presence of Ca2+ ions was established. • Two phase transitions occur in the sol–gel transition diagram for the κ-carrageenan–Ca2+ system. • Ca2+ ions preferred coordination five and six to associate with κ-carrageenan chains. • The presence of intra- and intermolecular hydrogen bonds facilitate associations between κ-carrageenan chains. [ABSTRACT FROM AUTHOR]