Human L-Dopa decarboxylase interaction with annexin V and expression during apoptosis.

l-Dopa Decarboxylase (DDC) is a pyridoxal requiring enzyme that catalyzes the decarboxylation of L-3,4-dihydroxyphenylalanine (l-Dopa) to Dopamine (DA). The function of DDC in physiological and pathological biochemical pathways remains poorly understood, while the function and regulation of human DDC isoforms is almost completely elusive. We have shown that Annexin V, a fundamental apoptosis marker, is an inhibitor of l-Dopa decarboxylase activity. Here we show the interaction of both the full-length DDC and the truncated isoform alternative DDC (Alt-DDC) with Annexin V in human tissue and cell lines. Interestingly, DDC isoform expression is enhanced or remains unaffected following staurosporine (STS) treatment, despite increased levels of cytotoxicity and apoptosis. The findings presented here provide novel insights concerning the involvement of DDC in programmed cell death.

Evidence for L-Dopa Decarboxylase Involvement in Cancer Cell Cytotoxicity Induced by Docetaxel and Mitoxantrone.

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.