Enhancement of docetaxel-induced cytotoxicity and apoptosis by all-trans retinoic acid (ATRA) through downregulation of survivin (BIRC5), MCL-1 and LTbeta-R in hormone- and drug resistant prostate cancer cell line, DU-145

doi:10.1186/1756-9966-27-37

Journal of Experimental & Clinical Cancer Research

Volume 27

Viewing options:

Abstract
Full text
PDF (352KB)

Associated material:

Related literature:

Articles citing this article
on Google Scholar
on ISI Web of Science
on PubMed Central
Other articles by authors
on Google Scholar

Kucukzeybek Y
Gul MK
Cengiz E
Erten C
Karaca B
Gorumlu G
Atmaca H
Uzunoglu S
Karabulut B
Sanli UA
Uslu R

on PubMed

Kucukzeybek Y
Gul MK
Cengiz E
Erten C
Karaca B
Gorumlu G
Atmaca H
Uzunoglu S
Karabulut B
Sanli UA
Uslu R
Related articles/pages
on Google

on Google Scholar

on PubMed

Tools:

Post to:

Research

Enhancement of docetaxel-induced cytotoxicity and apoptosis by all-trans retinoic acid (ATRA) through downregulation of survivin (BIRC5), MCL-1 and LTbeta-R in hormone- and drug resistant prostate cancer cell line, DU-145

Yuksel Kucukzeybek¹^* , Mustafa K Gul¹^* , Ercument Cengiz¹^* , Cigdem Erten¹^* , Burcak Karaca¹^* , Gurbuz Gorumlu¹^* , Harika Atmaca²^* , Selim Uzunoglu²^* , Bulent Karabulut¹^* , Ulus A Sanli¹^* and Ruchan Uslu¹

¹Division of Medical Oncology, Tulay Aktas Oncology Hospital, School of Medicine, Ege University, Bornova, Izmir, Turkey

²Section of Molecular Biology, Department of Biology, Faculty of Science and Arts, Celal Bayar University, Muradiye, Manisa, Turkey

author email corresponding author email* Contributed equally

Journal of Experimental & Clinical Cancer Research 2008, 27:37doi:10.1186/1756-9966-27-37


Published:	12 September 2008

Abstract

Background

The management of hormone-refractory prostate cancer (HRPC) still remains as an important challenge of daily oncology practice. Docetaxel has proved to be a first line treatment choice. All-trans retinoic acid (ATRA) could potently inhibit the growth of prostate cancer cells in vitro and its combination with various anticancer agents results in increased cytotoxicity. Based on these data, our aim was to examine the synergistic/additive cytotoxic and apoptotic effects of combination of docetaxel and ATRA, in hormone- and drug refractory human DU-145 prostate cancer cells. Furthermore, we have searched for the underlying mechanisms of apoptosis by demonstrating apoptosis-related genes.

Methods

XTT cell proliferation assay was used for showing cytotoxicity. For verifying apoptosis, both DNA Fragmentation by ELISA assay and caspase 3/7 activity measurement were used. For detecting the mechanism of apoptosis induced by docetaxel-ATRA combination, OligoGeArray^®which consists of 112 apoptosis related genes was used.

Results

Our results revealed that docetaxel and ATRA were synergistically cytotoxic and apoptotic in DU-145 cells, in a dose- and time dependent manner. It was also shown by our studies that apoptosis was induced in DU-145 prostate carcinoma cells with significant cytotoxicity, no matter which agent applied first. We have found out that docetaxel-ATRA combination significantly downregulates survivin (BIRC5), myeloid cell leukemia-1 (MCL-1) and lymphotoxin β-receptor (LTβR) genes, which all three have pivotal roles in regulation of apoptosis and cell cycle progression.

Conclusion

In conclusion, we strongly suggest that docetaxel and ATRA combination is a good candidate for this challenging era of daily oncologic practice. Also, the combination of docetaxel and ATRA might allow a reduction in docetaxel doses and by this way may diminish docetaxel adverse effects while maintaining the therapeutic effect in patients with HRPC.