Nitric oxide and its derivatives in the cancer battlefield.

Elevated levels of reactive nitrogen species, alteration in redox balance and deregulated redox signaling are common hallmarks of cancer progression and chemoresistance. However, depending on the cellular context, distinct reactive nitrogen species are also hypothesized to mediate cytotoxic activity and are thus used in anticancer therapies. We present here the dual face of nitric oxide and its derivatives in cancer biology. Main derivatives of nitric oxide, such as nitrogen dioxide and peroxynitrite cause cell death by inducing protein and lipid peroxidation and/or DNA damage. Moreover, they control the activity of important protein players within the pro- and anti-apoptotic signaling pathways. Thus, the control of intracellular reactive nitrogen species may become a sophisticated tool in anticancer strategies.

PTP1B phosphatase as a novel target of oleuropein activity in MCF-7 breast cancer model.

Phosphatase PTP1B has become a therapeutic target for the treatment of type 2-diabetes, whereas recent studies have revealed that PTP1B plays a pivotal role in pathophysiology and development of breast cancer. Oleuropein is a natural, phenolic compound with anticancer activity. The aim of this study was to address the question whether PTP1B constitutes a target for oleuropein in breast cancer MCF-7 cells. The cellular MCF-7 breast cancer model was used in the study. The experiments were performed using cellular viability tests, Elisa assays, immunoprecipitation, flow cytometry analyses and computer modelling. Herein, we evidenced that the reduced activity of phosphatase PTP1B after treatment with oleuropein is strictly correlated with decreased MCF-7 cellular viability and cell cycle arrest. These results provide new insight into further research on oleuropein and possible role of the compound in adjuvant treatment of breast cancer.

2-Methoxyestradiol and Its Combination with a Natural Compound, Ferulic Acid, Induces Melanoma Cell Death via Downregulation of Hsp60 and Hsp90.

Melanoma is an aggressive type of skin cancer with one of the highest mortality rates. Notably, its incidence in the last few decades has increased faster than any other cancer. Therefore, searching for novel anticancer therapies is of great clinical importance. In the present study, we investigated the anticancer potential of 2-methoxyestradiol, potent chemotherapeutic, in the A375 melanoma cellular model. In order to furthermore evaluate the anticancer efficacy of 2-methoxyestradiol, we have additionally combined the treatment with a naturally occurring polyphenol, ferulic acid. The results were obtained using the melanoma A375 cellular model. In the study, we used MTT assay, flow cytometry, and western blot techniques. Herein, we have evidenced that the molecular mechanism of action of 2-methoxyestradiol and ferulic acid is partly related to the reduction of Hsp60 and Hsp90 levels and the induction of nitric oxide in the A375 melanoma cell model, while no changes were observed in Hsp70 expression after 2-methoxyestradiol and ferulic acid treatment separately or in combination. This is especially important in case of chemoresistance mechanisms because the accumulation of Hsp70 reduces induction of cancer cell death, thus decreasing antitumour efficacy.