An increasing resistance of mammalian tumor cells to chemotherapy along with the severe side effects of commonly used cytostatics has raised the urgency in the search for new anti-cancer agents. Several drugs originally approved for indications other than cancer treatment have recently been found to have a cytostatic effect on cancer cells. These drugs could be expediently repurposed as anti-cancer agents, since they have already been tested for toxicity in humans and animals. The groups of newly recognized potential cytostatics discussed in this review include benzimidazole anthelmintics (albendazole, mebendazole, flubendazole), anti-hypertensive drugs (doxazosin, propranolol), psychopharmaceuticals (chlorpromazine, clomipramine) and antidiabetic drugs (metformin, pioglitazone). All these drugs have a definite potential to be used especially in combinations with other cytostatics; the chemotherapy targeting of multiple sites now represents a promising approach in cancer treatment. The present review summarizes recent information about the anti-cancer effects of selected drugs commonly used for other medical indications. Our aim is not to collect all the reported results, but to present an overview of various possibilities. Advantages, disadvantages and further perspectives regarding individual drugs are discussed and evaluated.

The sesquiterpenes β-caryophyllene, β-caryophyllene oxide (CAO), α-humulene (HUM), trans-nerolidol (NER), and valencene (VAL) are substantial components of the essential oil from Myrica rubra leaves which has exhibited significant antiproliferative effects in several intestinal cancer cell lines, with CaCo-2 cells being the most sensitive. The present study was designed to evaluate the effects of these sesquiterpenes on the efficacy and toxicity of the anticancer drug doxorubicin (DOX) in CaCo-2 cancer cells and in primary culture of rat hepatocytes. Our results showed that HUM, NER, VAL and CAO inhibited proliferation of CaCo-2 cancer cells but they did not affect the viability of hepatocytes. CAO, NER and VAL synergistically potentiated the efficacy of DOX in cancer cells killing. All sesquiterpenes exhibited the ability to selectively increase DOX accumulation in cancer cells and did not affect DOX concentration in hepatocytes. Additionally, CAO and VAL were able to increase the pro-oxidative effect of DOX in CaCo-2 cells. Moreover, CAO mildly ameliorated DOX toxicity in hepatocytes. Based on all results, CAO seems to be the most promising compound for further testing.

Glutathione peroxidases (GPxs) belong to the eight-member family of phylogenetically related enzymes with different cellular localization, but distinct antioxidant function. Several GPxs are important selenoproteins. Dysregulated GPx expression is connected with severe pathologies, including obesity and diabetes. We performed a comprehensive bioinformatic analysis using the programs miRDB, miRanda, TargetScan, and Diana in the search for hypothetical microRNAs targeting 3′untranslated regions (3´UTR) of GPxs. We cross-referenced the literature for possible intersections between our results and available reports on identified microRNAs, with a special focus on the microRNAs related to oxidative stress, obesity, and related pathologies. We identified many microRNAs with an association with oxidative stress and obesity as putative regulators of GPxs. In particular, miR-185-5p was predicted by a larger number of programs to target six GPxs and thus could play the role as their master regulator. This microRNA was altered by selenium deficiency and can play a role as a feedback control of selenoproteins’ expression. Through the bioinformatics analysis we revealed the potential connection of microRNAs, GPxs, obesity, and other redox imbalance related diseases.