Cancer and cardiovascular diseases are recently the most major health problems in the society of industrialized countries. As a result of increase of average lifetime, pollution of environment, inappropriate diet and lifestyle, the frequency of incidences of these diseases is still increasing. The difficulties with early diagnosis and the lack of efficient therapy leads to increased mortality.  Clinitians and scientists alike are constantly looking for new therapy approaches, new molecules and new delivery vehicles of already approved drugs to improve the efficiency of current therapeutic tools in malignant tumors.

Phenothiazine and its derivatives are wildely used as antipsychotics. It is well known that they have antiprion, antiviral, antibacterial and antiprotozoan properties. Futhermore, their ability to inhibit proliferation and to induce apoptosis in tumor cells implies their potential utilization in cancer treatment.

The aim of this study was to define the influence of derivatives of phenothiazine on cancer cells.

Two cells lines purchased from American Type Culture Collection (ATCC) were used: amelanotic melanoma C-32 and breast cancer MDA-MB-231 cells. We analysed the impact of two newly sythethized derivatives of phenothiazine prepared in Department of Organic Chemistry of School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec which were considered the anticancer agents. To mesure their cytotoxic and antiproliferative effects we performed assays on cell cultures treated by examinated molecules and on cells after incubation with approved cytostatic drugs: cisplatine and doxorubicine (reference semples). We analyse the expression of genes involved in regulation of cell cycle (TP53, CDKN1A) and genes controlling intrinsic pathway of apoptosis (BAX BCL-2). The influence of these derivates on activity of antioxydative enzymes were studied as well.

We demonstrated that the examined molecules have the cytotoxic and antiproliferative properties on two tested cells lines. The incubation of these cells with derivatives of phenothiazine at the concentration of 0,5 ug/ml leads to change in amount of mRNA encoding regulators of cell cycle: TP53, CDKN1A, genes involved in mitochondrial pathway of apoptosis: BAX i BCL-2 and genes encoding enzymes SOD, CAT i GPX. Increased BAX/BCL-2 ratio in MDA-MB-231 treated with studied drugs and cisplatin suggests that these substances act via intrinsic pathway of apoptosis.

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