galangin and Kidney-Neoplasms

Galangin, bioflavonoids, has been shown anti-cancer properties in various cancer cells. In this study, we investigated whether galangin could enhance TRAIL-mediated apoptosis in TRAIL resistant renal carcinoma Caki cells. Galangin alone and TRAIL alone had no effect on apoptosis, while combined treatment with galangin and TRAIL significantly induced apoptosis in renal carcinoma (Caki, ACHN and A498) but not normal cells (normal mouse kidney cells and human normal mesangial cells). Galangin induced down-regulation of Bcl-2 protein at the transcriptional level via inhibition of NF-κB activation but not p53 pathway. Furthermore, galangin induced down-regulation of cFLIP, Mcl-1 and survivin expression at the post-translational levels, and the over-expression of Bcl-2, cFLIP, Mcl-1 and survivin markedly reduced galangin-induced TRAIL sensitization. In addition, galangin increased proteasome activity, but galangin had no effect on expression of proteasome subunits (PSMA5 and PSMD4). In conclusion, our investigation suggests that galangin is a potent candidate for sensitizer of TRAIL resistant cancer cell therapy.

Topics: Antineoplastic Agents; Apoptosis; Carcinoma, Renal Cell; CASP8 and FADD-Like Apoptosis Regulating Protein; Cell Line, Tumor; Down-Regulation; Drug Screening Assays, Antitumor; Drug Synergism; Flavonoids; Gene Expression Regulation, Neoplastic; Humans; Inhibitor of Apoptosis Proteins; Kidney Neoplasms; Myeloid Cell Leukemia Sequence 1 Protein; NF-kappa B; Proteasome Endopeptidase Complex; Protein Processing, Post-Translational; Proto-Oncogene Proteins c-bcl-2; Survivin; TNF-Related Apoptosis-Inducing Ligand; Transcription, Genetic

Galangin, a flavonoid extracted from the root of the Alpinia officinarum Hence, has been shown to have anticancer properties against several types of cancer cells. However, the influence of galangin on human renal cancer cells remains to be elucidated. In the present study, proliferation of 786‑0 and Caki‑1 cells was suppressed following exposure to various doses of galangin. Cell invasion and wound healing assays were used to observe the effect of galangin on invasion and migration. The results demonstrated that Galangin inhibited cell invasion by suppressing the epithelial mesenchymal transition (EMT), with an increase in the expression of E‑cadherin and decreased expression levels of N‑cadherin and vimentin. The apoptosis induced by galangin was analyzed by flow cytometry. The results revealed that galangin induced apoptosis in a dose‑dependent manner. The accumulation of reactive oxygen species (ROS) is an important contributing factor for the apoptosis of various types of cancer cell. The dichlorofluorescein-diacetate method was used to determine the level of ROS. Galangin induced the accumulation of intracellular ROS and malondialdehyde, and decreased the activities of total antioxidant and superoxide dismutase in renal cell carcinoma cells. Galangin exerted an antiproliferative effect and inhibited renal cell carcinoma invasion by suppressing the EMT. This treatment also induced apoptosis, accompanied by the production of ROS. Therefore, the present data suggested that galangin may have beneficial effects by preventing renal cell carcinoma growth, inhibiting cell invasion via the EMT and inducing cell apoptosis.

Topics: Apoptosis; Carcinoma, Renal Cell; Cell Line, Tumor; Epithelial-Mesenchymal Transition; Flavonoids; Humans; Kidney Neoplasms; Neoplasm Invasiveness; Reactive Oxygen Species