The bacterial protein azurin enhances sensitivity of oral squamous carcinoma cells to anticancer drugs.

PURPOSE: Surgical therapy is the primary treatment for oral cancer, but it can cause facial distortion. Therefore, if anticancer drugs are effective against oral cancer, they may be used preferentially. However, oral squamous carcinoma cells (OSCCs) are resistant to these drugs, so finding a way to enhance the sensitivity of these cells to anticancer drugs is important. The bacterial protein azurin is known to selectively enter cancer cells and induce apoptosis. In this study, we show the anticancer effect of azurin in OSCC. MATERIALS AND METHODS: OSCC cell line (YD-9) was subjected to azurin treatment. Cell viability, morphology and protein expression levels were monitored after treatment of azurin. Cells were also subjected to combination treatment of azurin with either 5-fluorouracil or etopside. RESULTS: Azurin-treated cells showed decreased cell viability accompanied by apoptotic phenotypes including morphological change, DNA breakage, and increases in p53 and cyclin B1 protein levels. Combination treatment of azurin with other anti-tumor agents caused an increase in sensitivity to anticancer drugs in azurin-treated YD-9 cells. CONCLUSION: Azurin has a strong synergistic anticancer effect on oral cancer cells when it is used along with anticancer drugs.

The Bacterial Protein Azurin Enhances Sensitivity of Oral Squamous Carcinoma Cells to Anticancer Drugs

PURPOSE: Surgical therapy is the primary treatment for oral cancer, but it can cause facial distortion. Therefore, if anticancer drugs are effective against oral cancer, they may be used preferentially. However, oral squamous carcinoma cells (OSCCs) are resistant to these drugs, so finding a way to enhance the sensitivity of these cells to anticancer drugs is important. The bacterial protein azurin is known to selectively enter cancer cells and induce apoptosis. In this study, we show the anticancer effect of azurin in OSCC. MATERIALS AND METHODS: OSCC cell line (YD-9) was subjected to azurin treatment. Cell viability, morphology and protein expression levels were monitored after treatment of azurin. Cells were also subjected to combination treatment of azurin with either 5-fluorouracil or etopside. RESULTS: Azurin-treated cells showed decreased cell viability accompanied by apoptotic phenotypes including morphological change, DNA breakage, and increases in p53 and cyclin B1 protein levels. Combination treatment of azurin with other anti-tumor agents caused an increase in sensitivity to anticancer drugs in azurin-treated YD-9 cells. CONCLUSION: Azurin has a strong synergistic anticancer effect on oral cancer cells when it is used along with anticancer drugs.

[Selective inducement effect of bacterial redox protein azurin on apoptosis of human osteosarcoma cell line U2OS].

BACKGROUND & OBJECTIVE: Bacterial redox protein azurin can selectively inhibit proliferation, and induce apoptosis in various human cancer cells. These in vitro findings have been confirmed in vivo in nude mice bearing tumor xenograft. Furthermore, azurin could diminish tumor volume in nude mice bearing tumor xenograft with no evidence of toxicity. The mechanism of its action is unknown. This study was designed to explore the effects of azurin on apoptosis of osteosarcoma cell line U2OS, and its molecular mechanism. METHODS: U2OS cells were cultured with different concentrations of azurin. Cell viability was detected by MTT assay. The 50% inhibitory concentration (IC(50)) of azurin was calculated by Bliss method. Apoptotic morphology and apoptotic body of U2OS cells were observed under fluorescent microscope, and transmission electron microscope. DNA ladder was observed through agarose gel electrophoresis. Cell apoptosis was determined by flow cytometry (FCM). Protein levels of Bax, Bcl-2, and Caspase-3 were quantified by Western blot. RESULTS: Azurin inhibited growth and induced apoptosis of U2OS cells in a dose-dependent manner 48 h after treatment, with the IC(50) of(114.54+/-7.65) mg/L. Moreover, its inhibitory effect was significantly higher on U2OS cells than on MG63 cells or L-02 cells under the same concentrations (P<0.05). When treated with 100 or 200 mg/L of azurin for 24 h, U2OS cells showed typical apoptotic morphology, typical DNA ladder bands were observed. No apoptotic feature was observed in control cells. Sub-G1 peak and apoptotic peak of U2OS cells were observed when exposed to 200 mg/L of azurin for 48 h with the apoptosis index of 35.8%, cell cycle was arrested in G1 phase. Bcl-2 was down-regulated when U2OS cells were treated with azurin for 24 h, while Bax and caspase-3 were up-regulated. CONCLUSIONS: Azurin could selectively induce apoptosis of human osteosarcoma U2OS cells. The induction of apoptosis by azurin may be closely associated with down-regulation of Bcl-2, up-regulation of Bax, and activation of Caspase-3.