Cortex moutan induces bladder cancer cell death via apoptosis and retards tumor growth in mouse bladders

Source Lin M-Y, Lee Y-R, Chiang S–Y, et al. Complementary and Alternative Medicine. Volume 2013 (2013) http://dx.doi.org/10.1155/2013/207279       Cortex Moutan is the root bark of Paeonia suffruticosa Andr. It is the herbal medicine widely used in Traditional Chinese Medicine for the treatment of blood-heat and blood-stasis syndrome. Furthermore, it has been reported that Cortex Moutan has anticancer effect. In this study, the Cortex Moutan extract was evaluated in bladder cancer therapy in vitro and in vivo. Cortex Moutan extract reduces cell viability with IC50 between 1~2?mg/ml in bladder cancer cells, and it has lower cytotoxicity in normal urotheliums. It arrests cells in G1 and S phase and causes phosphatidylserine expression in the outside of cell membrane. It induces caspase-8 and caspase-3 activation and poly(ADP-ribose) polymerase degradation. The pan caspase inhibitor z-VAD-fmk reverses Cortex Moutan-induced cell death. Cortex Moutan also inhibits cell invasion activity in 5637 cells. In mouse orthotopic bladder cancer model, intravesical application of Cortex Moutan decreases the bladder tumor size without altering the blood biochemical parameters. In summary, these results demonstrate the antiproliferation and anti-invasion properties of Cortex Moutan in bladder cancer cells and its antibladder tumor effect in vivo. Cortex Moutan may provide an alternative therapeutic strategy for the intravesical therapy of superficial bladder cancer. Cortex Moutan (CM, root bark of Paeonia suffruticosa Andr.), named Mu Dan Pi in Chinese, is the herbal medicine widely used in Traditional Chinese Medicine (TCM). It tastes bitter and pungent. According to TCM theory, it belongs to the light cold-type medicine and has the function of heat-clearing, promoting blood circulation, removing blood stasis, cooling the blood, and reducing the deficient heat. In clinical regimen, CM is usually used to treat heat in the blood and blood stasis syndromes. It is used as an analgesic (Tatsumi et al., 2004), antispasmodic, antiaggregatory (Hirai, Terano & Hamazaki, 1983; Lin et al., 1999) and antioxidative agent (Yoshikawa et al., 2000). In other reports, CM itself or its major component has been shown to treat various disorders like diabetes (Lau et al., 2007), Alzheimer’s disease (Fujiwara et al., 2009; Zhou et al., 2011), arthritis (Kim et al., 2012), inflammation (Chou, 2003; Wu & Gu, 2009), sepsis, brain ischemia-reperfusion injury (Hsieh et al., 2006), HIV infection (Au et al., 2001), and herpes simplex virus infection (Hsiang et al., 2001). Recently, there are also some reports showing the anitumor activity of CM, including renal carcinoma (Wang et al., 2012), DLD-1 human colon cancer cells (Xing et al., 2010), and gastric cancer (Choi et al., 2012). In addition, one component of CM, paeoniflorin, was reported to have antitumor effect through apoptosis in lung cancer cells (Hung et al., 2008). Bladder cancer is a common malignancy worldwide (Parkin, 2008). More than 90% of bladder cancers are transitional cell carcinoma (TCC) in the histology, and it is classified into two groups in the pathogenesis: nonmuscle invasive and muscle invasive (Babjuk et al., 2011). There are two groups of intravesical therapeutic agents for bladder cancer therapy. Bacillus Calmette-Guérin (BCG) is the immunotherapeutic agent, and mitomycin C is one of the chemotherapeutic agents (Babjuk et al., 2011; Manoharan, 2011). Up to now, Bacillus Calmette-Guérin (BCG), a immunotherapeutic agent and mitomycin C is one of the chemotherapeutic agents, which provokes considerable and sometimes serious side effects, and the recurrence rate remains high in spite of intravesical chemotherapy. There is certainly place for improvement in bladder cancer therapy. 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