Sesquiterpene lactones (SLs) are plant-derived compounds that are abundant in plants of the Asteraceae family and posses a broad spectrum of biological activities, ranging from anti-inflammatory, phytotoxic, antibacterial, and antifungal to cytotoxic/anticancer. In recent years, anticancer properties of these compounds and molecular mechanisms of their action have been studied extensively on numerous cell lines and also on experimental animals. SLs have been shown to disrupt cellular redox balance and induce oxidative stress in cancer cells. Oxidative stress is associated with increased production of reactive oxygen species (ROS) which in turn can promote many aspects of cancer development and progression. On the other hand, ROS, which initiate apoptosis via the mitochondrial-dependent pathway, can also be used to kill cancer cells, if they can be generated in cancer. One of the most important regulators of the redox equilibrium in the cells is reduced glutathione (GSH). In cancer cells, GSH levels are higher than in normal cells. Therefore, SL can induce apoptosis of cancer cells by decreasing intracellular GSH levels. The use of SL which can affect intracellular redox signaling pathways can be considered an interesting approach for cancer treatment. In this review, we give a brief description of the mechanisms and pathways involved in oxidative stress-induced anticancer activity of SL.

Cancer is one of the leading causes of mortality in the developed countries. The search for novel drug candidates is a priority goal for cancer therapy. However, the emergence of drug resistance reduces the effectiveness of new medications. The ATP binding cassette (ABC) family of proteins are efflux pumps that transport various structurally unrelated and potentially dangerous substances out of the cells. These transporters have evolved as a complex cellular defense system, for the recognition and removal of toxic agents entering the cells from their environment. Several of the ABC transporters are related to chemoresistance in cancer therapy, as the rapidly dividing malignant cells use them to protect themselves from medical interventions. Here we review the members of the ABC transporter families responsible for the multidrug resistance in anticancer therapy.

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New chiral camphane-derived benzisoselenazol-3(2H)-ones and corresponding diselenides have been synthetized using a convenient one-pot procedure. Se-N bond was efficiently converted to an Se-Se bond, which could also be easily re-oxidized to the initial benzisoselenazolone moiety. The antioxidant activity of camphor derivatives was evaluated and compared to the reactivity of a series of N-amino acid benzisoselenazol-3(2H)-ones obtained by a modified procedure involving the improved synthesis and isolation of the diseleno bis(dibenzoic) acid. The most efficient peroxide scavengers, N-bornyl and N-leucine methyl ester benzisoselenazol-3(2H)-ones, were further evaluated as cytotoxic agents on four cancer cell lines (MCF-7, HEP G2, HL 6, and DU 145) and normal cell line PNT1A. The highest antiproliferative potential was evaluated for two compounds bearing a 3-methylbutyl carbon chain, N-leucine methyl ester and N-3-methylbutyl benzisoselenazol-3(2H)-ones.

Renalase decreases circulating catecholamines concentration and is important in maintaining primary cellular metabolism. Renalase acts through the plasma membrane calcium ATPase 4b in the heart, which affects pressure overload but not exercise induced heart hypertrophy. The aim of this study was to test the association between a functional polymorphism Glu37Asp (rs2296545) of the renalase gene and left ventricular hypertrophy in a large cohort of patients with aortic stenosis. The study group consisted of 657 patients with aortic stenosis referred for aortic valve replacement. Preoperative echocardiographic assessment was performed to obtain cardiac phenotypes. Generalized-linear models were implemented to analyze data using crude or full model adjusted for selected clinical factors. In females, the Asp37 variant of the Glu37Asp polymorphism was associated with higher left ventricular mass (p = 0.0021 and p = 0.055 crude and full model respectively), intraventricular septal thickness (p = 0.0003 and p = 0.0143) and posterior wall thickness (p = 0.0005 and p = 0.0219) all indexed to body surface area, as well as relative wall thickness (p = 0.001 and p = 0.0097). No significant associations were found among the male patients. In conclusion, we have found the association of the renalase Glu37Asp polymorphism with left ventricle hypertrophy in large group of females with aortic stenosis. The Glu37Asp polymorphism causes not only amino-acid substitution in FAD binding domain but may also change binding affinity of the hypoxia- and hypertrophy-related transcription factors and influence renalase gene expression. Our data suggest that renalase might play a role in hypertrophic response to pressure overload, but the exact mechanism requires further investigation.