Title:Evidence for L-Dopa Decarboxylase Involvement in Cancer Cell Cytotoxicity Induced by Docetaxel and Mitoxantrone
Volume: 19
Issue: 13
Author(s): Evangelos D. Kalantzis, Andreas Scorilas and Dido Vassilacopoulou*
Affiliation:
- Department of Biochemistry and Molecular Biology, National and Kapodistrian University of Athens, Athens,Greece
Keywords:
DDC, alternative isoforms, prostate cancer, breast cancer, cell death, apoptosis.
Abstract: Background: L-Dopa decarboxylase (DDC) expression has been implicated in the biochemistry
of several human cancers. Docetaxel and Mitoxantrone are two widely used anticancer agents.
Docetaxel is a semi-synthetic analogue of Paclitaxel, an extract from the bark of the rare Pacific yew
tree Taxus brevifolia, and Mitoxantrone is an anthracenedione anticancer agent.
Objective: The purpose of the present study was to investigate the effect of chemotherapeutic agents on
the expression of human DDC in human prostate and human breast cancer cell lines. Furthermore, the
study focused on the effect of chemotherapeutics - particularly Docetaxel and Mitoxantrone – on the
viability of mammalian cells expressing human DDC protein isoforms.
Methods: We investigated the effect of Docetaxel and Mitoxantrone on the expression of DDC in DU-
145 (androgen-independent prostate cancer cell line) and MCF-7 (human breast adenocarcinoma cell
line). In order to gain insight into the effect of DDC on cell viability following chemotherapeutic agent
treatment, we investigated the cytotoxicity and apoptosis levels on CHO cells expressing different human
DDC protein isoforms.
Results: Our obtained data indicated that exposure of DU-145 and MCF-7 cells to Docetaxel and Mitoxantrone
enhances the expression of neural type DDC mRNA isoforms. Interestingly, DDC protein
levels were not affected, despite the cytotoxic events elicited by the chemotherapeutic agent treatment.
Moreover, expression of DDC and its alternative protein isoforms, appear to enhance the cytotoxic and
apoptotic events conferred by exposure to Docetaxel and Mitoxantrone.
Conclusion: This study suggests the possible involvement of DDC expression in Docetaxel and Mitoxantrone-
induced cytotoxicity and apoptosis.