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Asian Journal of Andrology (2010) 12: 390-399. doi: 10.1038/aja.2009.87; published online 18 January 2010.
Inhibition of proliferation of prostate cancer cell line, PC-3, in vitro and in vivo using (−)-gossypol
Xian-Qing Zhang1,2,*, Xiao-Feng Huang3,*, Shi-Jie Mu2, Qun-Xing An2, Ai-Jun Xia2, Rui Chen2 and Dao-Cheng Wu1
1 The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Xi'an Jiaotong University, Xi'an 710038, China
2 Department of Blood Transfusion, Xijing Hospital, Xi'an 710032, China
3 Central Laboratory, Fourth Military Medical University, Xi'an 710032, China
Correspondence: Prof. Dao-Cheng Wu, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Xi'an Jiaotong University, 28 West Xianning Road, Xi'an 710038, China. Fax: +86-29-8266-3941 E-mail: wudaocheng@mail.xjtu.edu.cn
* These authors contributed equally to this work.
Received 8 June 2009; Revised 7 September 2009; Accepted 24 November 2009; Published online 18 January 2010.
| Abstract |
We investigated the antiproliferative activity of (−)-gossypol on the human prostate cancer cell line PC3 in vitro and in vivo to elucidate its potential molecular mechanisms. Cell growth and viability were evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and cell apoptosis was detected by flow cytometry, terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) and electron microscopy. Expression of proliferating cell nuclear antigen (PCNA), Bcl-2, CD31, caspase-3 and caspase-8 in tumour tissue was determined by immunohistochemistry. The drug concentration that yielded 50% cell inhibition (IC50 value) was 4.74 μg mL−1. In the PC-3 tumour xenograft study, (−)-gossypol (> 5 mg kg−1) given once a day for 7 days significantly inhibited tumour growth in a dose-dependent manner. Immunohistochemical analysis revealed that (−)-gossypol enhanced caspase-3 and caspase-8 expression and decreased the expression of PCNA, Bcl-2 and CD31 in tumour tissues. It suggested that cell apoptosis and inhibition of angiogenesis might contribute to the anticancer action of (−)-gossypol.
Keywords: apoptosis; electron microscopy; flow cytometry; (−)-gossypol; immunohistochemistry; prostate cancer |
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