γ­irradiated prednisolone promotes apoptosis of liver cancer cells via activation of intrinsic apoptosis signaling pathway.

Prednisolone is an anti­inflammatory drug used to treat a number of conditions, including liver disease and cancer. Numerous studies have demonstrated that glucocorticoids such as prednisolone modified by ionizing radiation can promote anticancer activity in cancer cells. To the best of our knowledge, however, the effect of ionizing radiation on prednisolone structure and cancer cells has not yet been identified. The present study created a novel prednisolone derivative using γ­irradiation, and its anticancer properties were investigated in liver cancer cells. The present study confirmed the structure of the new prednisolone derivative using liquid chromatogram­mass spectrometry. MTT assays determined the cytotoxic effects of γ­irradiated (IR)­prednisolone in liver cancer cells. Flow cytometry analysis evaluated apoptosis, mitochondrial membrane potential and cell cycle distribution. Western blotting was used to analyze the proteins associated with apoptosis. The chromatogram profile revealed that IR­prednisolone produced a number of peaks compared with the single peak of the original prednisolone. In contrast to prednisolone, the MTT results showed that IR­prednisolone significantly prevented the growth of liver cancer cells. IR­prednisolone promoted apoptosis and arrested the cell cycle at the G0/G1 stage in Huh7 cells. IR­prednisolone also altered the mitochondrial membrane potential and activated caspase­associated proteins, which activated the intrinsic apoptotic signaling pathway. In conclusion, IR­prednisolone promoted anticancer effects in liver cancer cells via apoptosis activation. The present study demonstrated that IR­prednisolone may be a potential anticancer agent against liver cancer, although specific molecules have yet to be identified.

Centipedegrass extracts regulate LPS-mediated aberrant immune responses by inhibiting Janus kinase.

BACKGROUND: Centipedegrass extract (CGE) is rich in several polyphenolic compounds including C-glycosylflavonoids, such as maysin and its derivatives, and exerts antioxidant, anti-adipogenic and anticancer effects. However, the effect of CGE on the immune system is unclear. PURPOSE: CGE might inhibit NO production induced by lipopolysaccharide (LPS). In this study, we propose a molecular mechanism for regulation of aberrant immune responses by CGE in LPS-stimulated RAW264.7 cells. STUDY DESIGN: We will preparation of Centipedegrass extract and purify partially in rich of maysin and its derivatives. And examine the effect of the CGE on immune system using LPS-induced RAW cells and animals. METHODS: LPS-induced nitric oxide (NO) and interleukin-6 levels were measured by enzyme-linked immunosorbent assay. The mRNA and protein levels of immune mediators were analyzed by reverse-transcription polymerase chain reaction and immunoblotting, respectively. RESULTS: CGE inhibited LPS-induced NO production in a concentration-dependent manner by suppressing inducible nitric oxide synthase (iNOS) expression in LPS-stimulated cells; this effect was mediated by inhibition of the JAK/STAT pathway. However, CGE did not regulate the expression of other factors, including phosphorylated p38, c-jun N-terminal kinase, or extracellular signal-regulated kinase 1/2. In addition, CGE increased T cells percentage in peripheral blood after oral administration. CONCLUSION: These results indicate that CGE suppresses LPS-induced production of NO and expression of iNOS by directly inhibiting JAK2 kinase activity and enhancing effects on the immune system in mice.

Kenalog modified by ionizing radiation induces intrinsic apoptosis mediated by elevated levels of reactive oxygen species in melanoma cancer.

Kenalog is a synthetic glucocorticoid drug used to treat various cancers including ocular and choroidal melanoma. However, the drug achieves rarely sustainable results for patients. To overcome this difficulty, the structure of Kenalog was altered by ionizing radiation (IR) to develop a more effective anticancer agent for treatment of various skin cancers. The anticancer effect of modified Kenalog (Kenalog­IR) was assessed in melanoma cancer cells in vitro. The assessment of mitochondrial functions by MTT assay revealed significant inhibition of melanoma cancer cell viability by Kenalog­IR compared to Kenalog. Moreover, Kenalog­IR­induced apoptotic cell death was associated with the intrinsic mitochondrial pathway by triggering the release of intrinsic apoptosis molecules through activation of caspase­related molecules in concentration and time­dependent manners. Furthermore, it was observed that Kenalog­IR­induced apoptosis was associated with the generation of reactive oxygen species (ROS) with increased G2/M cell cycle arrest. Collectively, Kenalog­IR may be a potential suppressor of skin­related cancer in particular melanoma cancer.

Dexamethasone modified by gamma-irradiation as a novel anticancer drug in human non-small cell lung cancer.

Dexamethasone (Dex) is widely used in the management of leukemia and lymphoma. While Dex is commonly used for hematological malignancies, the effects of Dex in solid cancer cells remain controversial. To develop a more effective anticancer drug for solid cancers, Dex was modified by ionizing radiation and the anticancer activity of ionizing-radiation-irradiated Dex (Dex-IR) was investigated in human lung cancer cells. Using the MTT assay, the proliferation of non-small cell lung cancer cells was significantly inhibited after treatment with Dex-IR compared with Dex. Furthermore, Dex-IR induced apoptotic cell death and cell cycle arrest of H1650 human lung cancer cells. The invasiveness of H1650 cells was significantly reduced and the matrix metalloproteinase activity was strongly suppressed. These results indicate that Dex-IR acts as a tumor suppressor by both inducing apoptosis and arresting the cell cycle. Although the structure of Dex-IR remains to be determined, our results suggest it may be useful as a novel anticancer agent for the treatment of solid cancers.