Comparison of salvianolic acid B and celecoxib effects on nontumorogenic BPH1 and tumorogenic BPH1^CAFTD1 human prostate cell lines Free

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Prostate cancer is the second most deadly cancer in American males. Finasteride and cycloxygenase-2 inhibitors are being evaluated in chemoprevention trials. Although clinical efficacy has previously been shown in the several prevention trials, many more trials have shown limited effect or even harm. Thus, there is an urgent need to develop effective, safe and affordable cancer-preventing agents. Salvia miltiorrhiza Bge (SMB) is a herb that has been used in traditional Chinese medicine for over thousand years to treat tumors without appreciable adverse effects. Based on the theory of traditional Chinese medicine, SMB reduces blood coagulation and inflammatory reactions associated with immune response. In this study, the cancer-preventing activities of salvianolic acid B (Sal-B, a dominant water soluble constituent of SMB) and celecoxib (a selective COX-2 inhibitor), were evaluated utilizing in nontumorogenic BPH1 and tumorogenic BPH1^CAFTD1 human prostate cell lines. Sal-B significantly inhibited the proliferation of both prostate cell lines in a dose-dependent fashion, while celecoxib was only moderately effective. Colony formation was decreased by more than 45% when the cells were exposed to 10 μg/ml of Sal-B for 24 hours in both prostate cell lines. Induction of apoptosis and cell cycle in the cell lines were also analyzed by flow cytometry. Sal-B treated cells showed the accumulation of a discrete population of signals under the sub G1 cell cycle region. This indicated that 46.23% of the cells underwent apoptosis after 12-hour treatment with Sal-B. About 56.15% of debris from dead cells was observed in the case of Sal-B treated cell suspension as opposed to only 17.81% in untreated cell suspension. The asymmetric transbilayer distribution was also lost in both prostate cell lines upon treatment with Sal-B. This was confirmed by using fluorescein tagged FITC annexin V. Moreover, growth inhibitory and apoptotic effects of Sal-B were stronger than those of celecoxib. The results from flow cytometry, Western blot and fluorescent imaging indicated that Sal-B significantly inhibited COX-2 expression in both prostate cell lines. Western blot analysis showed that Sal-B was a more potent inhibitor of COX-2 expression in both prostate cell lines. In conclusion, Sal B was more cytotoxic to nontumorogenic BPH1 cells and tumorogenic BPH1^CAFTD1 cells than celecoxib. (Supported in part by Tianjue Gu Foundation and grants P20 CA118770 from NCI/NIH and DAMD17-03-1-0123 from DoD)