Abstract
Bear bile was used as a traditional medicine or tonic in East Asia, and ursodeoxycholic acid (UDCA) is the most important compound in bear bile. Further, synthetic UDCA is also used in modern medicine and nutrition; therefore, its further functional effects warrant research, in vitro methods could be used for the fundamental research of its anticancer effects. In this study, the apoptotic effects of UDCA in human oral squamous carcinoma HSC-3 cells through the activation of caspases were observed by the experimental methods of MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide) assay, DAPI (4’,6-diamidino-2-phenylindole) staining, flow cytometry analysis, RT-PCR (reverse transcription-polymerase chain reaction) assay and Western blot assay after HSC-3 cells were treated by different concentrations of UDCA. With 0 to 400 μg/mL UDCA treatment, UDCA had strong growth inhibitory effects in HSC-3 cells, but had almost no effect in HOK normal oral cells. At concentrations of 100, 200 and 400 μg/mL, UDCA could induce apoptosis compared to untreated control HSC-3 cells. Treatment of 400 μg/mL UDCA could induce more apoptotic cancer cells than 100 and 200 μg/mL treatment; the sub-G1 DNA content of 400 μg/mL UDCA treated cancer cells was 41.3% versus 10.6% (100 μg/mL) and 22.4% (200 μg/mL). After different concentrations of UDCA treatment, the mRNA and protein expressions of caspase-3, caspase-8, caspase-9, Bax, Fas/FasL (Fas ligand), TRAIL (TNF-related apoptosis-inducing ligand), DR4 (death receptor 4) and DR5 (death receptor 5) were increased in HSC-3 cells, and mRNA and protein expressions of Bcl-2 (B-cell lymphoma 2), Bcl-xL (B-cell lymphoma-extra large), XIAP (X-linked inhibitor of apoptosis protein), cIAP-1 (cellular inhibitor of apoptosis 1), cIAP-2 (cellular inhibitor of apoptosis 2) and survival were decreased. Meanwhile, at the highest concentration of 400 μg/mL, caspase-3, caspase-8, caspase-9, Bax, Fas/FasL, TRAIL, DR4, DR5, and IκB-α expression levels were the highest, and Bcl-2, Bcl-xL, XIAP, cIAP-1, cIAP-2, survival, and NF-κB expression levels were the lowest. These results proved that UDCA could induce apoptosis of HSC-3 cancer cells through caspase activation, and the higher concentration of UDCA had stronger effects in vitro. UDCA might be a good nutrient for oral cancer prevention.
Highlights
In traditional Asian medicine, bear bile extracted from the gallbladder of Ursus thibetanus or Ursus arctos is considered a cure for various diseases
At concentrations ranging from 0 to 500 μg/mL of ursodeoxycholic acid (UDCA), chenodeoxycholic acid (CDCA) and deoxycholic acid (DCA), human oral squamous carcinoma HSC-3 cells and TCA8113 cell viabilities were decreased by UDCA, CDCA and DCA in a concentration-dependent manner
At a concentration of 500 μg/mL, inhibition of the HSC-3 cells treated with UDCA reached 100% and at a concentration of 400 μg/mL, inhibition of the HSC-3 cells treated with CDCA and DCA reached 100% (Figure 1A)
Summary
In traditional Asian medicine, bear bile extracted from the gallbladder of Ursus thibetanus or Ursus arctos is considered a cure for various diseases. With the development of modern medicine, it is found that the major active component in bear bile is ursodeoxycholic acid (UDCA) [1]. UDCA is a safe drug with no side effects and is widely used in the treatment of diseases, such as gallstones, primary cirrhosis, autoimmune hepatitis and colon cancer around the world [2]. From, for example, gingivitis and periodontitis, may be another cause of oral cancer [5]. Written in ancient Chinese medical books, bear bile can treat bacterial diseases through sterilization. Laboratory experiments further confirmed that the main component of bear bile, UDCA, has the effect of sterilization and inhibition of inflammation [1]
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