ABSTRACTS – ORAL PRESENTATIONS - AMCA, spol. s r.o.

proteins activity in HT-29 colon cancer cells.
We report here decreased level of protein BCRP and decrease activity after treatment
with 50 nM HY and HP or AR under the dark conditions after 16 h treatment, while no
significant changes of MRP1, MRP2 and P-gp were found. When evaluating HY alone or
combination of HY with AR (6 h after light-activation) decreased level of protein MRP2
was observed. The therapy with light-activated HY modulated by 5 μM HP showed
increased level of protein MRP1 and MRP2, in contrast to the decreased level of BCRP
and MRP2 protein after therapy HY or AR alone or HY/5μM AR. However the most
important analysis was transporter proteins activity which show decreased.
The cytochrome P450 3A4 (CYP3A4) is one of the most important enzymes involved in the
metabolism of xenobiotics in the human body. The protein level of CYP3A4 was increased
by HY, HP and AR therapy alone or in combination of HY/1μM HP. The subsequent analysis
of CYP3A4 proteins and mRNA 6 h after light-activation of HY therapy modulated by AR
showed significant decreased level of protein, similarly decreased of mRNA expression
and decreased of protein activity. We may conclude that pre-treatment with HP or AR
affected proteins level of BCRP, MRP1 and MRP2, what could be one of the mechanisms
responsible for pharmacokinetics of hypericin in HT-29 colon adenocarcinoma cells
leading to higher therapeutic efficiency of HY-PDT. The inhibitory effect of HP and AR to
activity of membrane transport proteins and to CYP3A4 protein also could be important
as therapeutic strategies in the treatment of cancer. The presented data may help to
elucidate the mechanisms of action for various bioactive constituents of St. John’s wort
possessing potential therapeutic properties.
Acknowledgements
This work was supported by the Slovak Research and Development Agency under the
contract No. APVV-0040-10 and the Scientific Grant Agency of the Ministry of Education
of the Slovak Republic under the contract No. VEGA 1/0626/11.
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