curcumin and gambogic-acid

Integrins are cell-matrix adhesion molecules providing both mechanical engagement of cell to extracellular matrix, and generation of cellular signals that are implicated in cancer malignancies. The concept that integrins play important roles in cell survival, proliferation, motility, differentiation, and ensuring appropriate cell localization, leads to the hypothesis that inhibition of certain integrins would benefit cancer therapy. In lung cancer, integrins αv, α5, β1, β3, and β5 have been shown to augment survival and metastatic potential of cancer cells. This review presents data suggesting integrins as molecular targets for anti-cancer approaches, and the mechanisms through which integrins confer resistance of lung cancer to chemotherapeutics and metastasis. The better understanding of these key molecules may benefit the discovery of anti-cancer drugs and strategies.

Topics: Antineoplastic Agents; Cell Adhesion; Cell Differentiation; Cell Proliferation; Cell Survival; Curcumin; Disease Progression; Extracellular Matrix; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Integrins; Lung Neoplasms; Neoplasm Metastasis; Ouabain; Phloretin; Xanthones

Gambogic acid (GA), a natural product with a xanthone structure, has a broad range of anti-proliferative effects on cancer cell lines. We evaluated GA for its cytotoxic effects on T98G glioblastoma cells. GA exhibited potent anti-proliferative activity and induced apoptosis in T98G glioblastoma cells in a dose-dependent manner. Incubation of cells with GA revealed apoptotic features including increased Bax and AIF expression, cytochrome c release, and cleavage of caspase-3, -8, -9, and PARP, while Bcl-2 expression was downregulated. Furthermore, GA induced reactive oxygen species (ROS) generation in T98G cells. Our results indicate that GA increases Bax- and AIF-associated apoptotic signaling in glioblastoma cells.

Topics: Antineoplastic Agents; Apoptosis; Brain Neoplasms; Caspase 3; Caspase 8; Caspase 9; Cell Line, Tumor; Cell Proliferation; Cytochromes c; Down-Regulation; Glioma; Humans; Proto-Oncogene Proteins c-bcl-2; Reactive Oxygen Species; Signal Transduction; Xanthones