Cancer therapy is challenging for scientists because of low effectiveness of so far existing
therapies (especially in case of great invasiveness and advanced
tumor stage). Such need for new
drug development and search for more efficient new findings in therapeutical applications is therefore still valid. There are also conducted studies on modifying so far existing drugs and their new methods of usage in oncology practice. One of them is
phenothiazine and its derivatives which are used in psychiatric treatment for years. They also exhibit antiprion,
antiviral, antibacterial and antiprotozoal properties. Cytotoxic activity, influence on proliferation, ability to induce apoptosis suggest also a possibility of
phenothiazine derivatives usage in
cancer cells termination. The aim of our the study was to evaluate the influence of two
amine derivatives of
phenothiazine on
cancer cells in vitro.
Amelanotic melanoma C-32 cell line (ATCC) and
glioma SNB-19 cells (DSMZ) were used in this study and two derivatives were analyzed. In view of examined substances
tumor potential toxicity cells proliferation and viability exposed to
phenothiazine derivatives were established. Cell cycle regulatory genes expression (TP53 and CDKN1A), S-phase marker--H3 gene and intracellular apoptosis pathway genes (BAX, BCL-2) were analyzed using RT-QPCR method. The influence of examined derivatives on total cell oxidative status (TOS), total antioxidative status (TAS),
malondialdehyde concentration (MDA) and
superoxide dismutase activity (SOD) were analyzed. As a result, examined
phenothiazine derivatives cytotoxic action on C-32 and SNB-19 and also cells proliferation inhibition were determined. Cell cycle regulatory genes (TP53, CDKN1A) expression and
protein products of genes involved in mitochondial apoptosis pathway (BAX, BCL-2) expression are changed by the presence of
phenothiazine derivatives during culturing. There were also noted small changes in redox potential in cells exposed to two mentioned
phenothiazine derivatives.