Abstract

Vitexicarpin (3', 5-dihydroxy-3, 4', 6, 7-tetramethoxyflavone), a polymethoxyflavone isolated from Viticis Fructus (Vitex rotundifolia Linne fil.), has long been used as an anti-inflammatory herb in traditional Chinese medicine. It has also been reported that vitexicarpin can inhibit the growth of various cancer cells. However, there is no report elucidating its effect on human prostate carcinoma cells. The aim of the present study was to examine the apoptotic induction activity of vitexicarpin on PC-3 cells and molecular mechanisms involved. MTT studies showed that vitexicarpin dose-dependently inhibited growth of PC-3 cells with an IC50~28.8 μM. Hoechst 33258 staining further revealed that vitexicarpin induced apoptotic cell death. The effect of vitexicarpin on PC-3 cells apoptosis was tested using prodium iodide (PI)/Annexin V-FITC double staining and flow cytometry. The results indicated that vitexicarpin induction of apoptotic cell death in PC-3 cells was accompanied by cell cycle arrest in the G2/M phase. Furthermore, our study demonstrated that vitexicarpin induction of PC-3 cell apoptosis was associated with upregulation of the proapoptotic protein Bax, and downregulation of antiapoptotic protein Bcl-2, release of Cytochrome c from mitochondria and decrease in mitochondrial membrane potential. Our findings suggested that vitexicarpin may become a potential leading drug in the therapy of prostate carcinoma.

Highlights

  • Prostate cancer is the second most common diagnosed cancer after lung cancer worldwide, and it is the third most common cause of cancer deaths in developed countries

  • The results indicated that vitexicarpin induction of apoptotic cell death in PC-3 cells was accompanied by cell cycle arrest in the G2/M phase

  • Effect of vitexicarpin on human prostate carcinoma PC-3 cell viabilities were determined using MTT assay

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Summary

Introduction

Prostate cancer is the second most common diagnosed cancer after lung cancer worldwide, and it is the third most common cause of cancer deaths in developed countries. In 2011, 240,890 men were diagnosed with prostate cancer and 33,720 men died of it as estimated by The American Cancer Society 2012. Prostate cancer incidence and mortality is comparatively higher in developed countries. Treatment of prostate cancer depends on age of patients, overall health of individual, and the stage of disease. Current available therapies include active surveillance, surgery, radiation therapy, hormone therapy, chemotherapy, and immunotherapy. Because prostate cancer can recur in an androgen-insensitive or hormone-refractory form that is not responsive to current therapies, the mortality rate associated with recurrent cases is high (American Cancer Society, 2012). There is great demand for effective novel therapeutic agents

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