[Frontiers In Bioscience, Elite, 9, 235-245, March 1, 2017]

Combinatorial effect of curcumin with docetaxel modulates apoptotic and cell survival molecules in prostate cancer

Saswati Banerjee1, Santosh K. Singh1, Indrajit Chowdhury2, James W. Lillard Jr1, Rajesh Singh1

1Department of Microbiology, Biochemistry and Immunology, 2Department of Obstetrics and Gynecology; Morehouse School of Medicine, 720 Westview drive, SW, Atlanta- 30310 USA

TABLE OF CONTENTS

1. Abstracts
2. Introduction
3. Materials and methods
3.1. Materials
3.2. Cell culture
3.3. MTT assay
3.4. Apoptosis assay
3.5. TUNEL assay
3.6. Western blot analysis
3.7. Statistical analysis
4. Results
4.1. Curcumin augments the cytotoxic effects of docetaxel in prostate cancer
4.2. Curcumin in combination with docetaxel enhances the apoptosis in PCa cells
4.3. Curcumin synergizes the apoptosis induced by docetaxel in PCa cells
4.4. Curcumin enhances pro-apoptotic marker expression in docetaxel-treated PCa cells
4.5. Curcumin blocks NF-κB activation in docetaxel-treated PCa cells
4.6. Curcumin synergizes the inhibition of oncogenic receptor tyrosine kinases and activation of tumor suppressor gene p53 in the docetaxel treated prostate cancer
5. Discussions
6. Acknowledgements
7. References

1. ABSTRACT

Docetaxel is the most commonly used chemotherapeutic agent to target androgen signaling in metastatic prostate cancer (PCa); however, prolonged treatment with docetaxel results in drug-resistant cancer cells. Combination therapies have the potential of increasing the effectiveness of drug treatment as well as decreasing the side effects. Curcumin is a nontoxic organic compound with multifaceted chemopreventive potential. In this study, we evaluated whether curcumin can reinforce the effect of docetaxel on PCa cells. The PCa cell lines DU145 and PC3 were treated with curcumin and docetaxel alone or in combination. After completion of the treatment cell proliferation and the expression of pro-survival and anti-apoptotic markers and the signaling molecules were analyzed. The combined treatment of curcumin and docetaxel inhibited the proliferation and induced apoptosis significantly higher than the curcumin and docetaxel-treated group alone. Interestingly, the combined treatment with curcumin and docetaxel modulates the expression of RTKs, PI3K, phospho-AKT, NF-kappa B, p53, and COX-2. These results suggest that curcumin can be a potential therapeutic contender in enhancing the efficacy of docetaxel in PCa treatment.

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Key Words: Curcumin, Prostate Cancer, Apoptosis, Docetaxel, EGFR, PI3K, Phospho-AKT, NF-kB, p53, COX-2

Send correspondence to: Rajesh Singh, Morehouse School of Medicine, Department of Microbiology, Biochemistry and Immunology, 720 Westview Drive SW, Atlanta GA 30310, Tel: 404-756-6661, Fax: 404-752-1179, E-mail: rsingh@msm.edu