Curcumin induces apoptosis and inhibits angiogenesis in murine malignant mesothelioma

Malignant pleural mesothelioma (MPM) is a rare form of cancer that is associated with asbestos exposure. Unfortunately, current therapies have limited efficacy. Previous studies have indicated that curcumin exerts antiproliferative and antitumor effects, and has low toxicity. The present study aimed to evaluate the anticancer effects of curcumin on the RN5 MPM cell line. The inhibitory effects of curcumin on cell viability were determined using the sulforhodamine B assay. In addition, cell cycle progression was analyzed by propidium iodide (PI) staining and flow cytometry, and curcumin-induced apoptosis was measured by Annexin V/PI double staining. The translocation of apoptosis-inducing factor (AIF) was assessed by western blotting and immunofluorescence, and the expression levels of the phosphoinositide 3-kinase (PI3K)-AKT serine/threonine kinase (Akt)-mammalian target of rapamycin (mTOR) signaling pathway proteins and mitochondria-associated proteins were evaluated by western blotting. In vivo antitumor effects were evaluated in a subcutaneous murine model. Briefly, tumors were harvested from the mice, and immunohistochemistry was conducted to evaluate cell proliferation, apoptosis and angiogenesis. The results indicated that curcumin inhibited RN5 cell viability and induced apoptotic cell death. In addition the findings suggested that curcumin-induced cell apoptosis occurred via the mitochondrial pathway, and caspase-independent and AIF-dependent pathways. Further analysis revealed that curcumin may act as a PI3K-Akt-mTOR signaling pathway inhibitor by downregulating PI3K, p-Akt, p-mTOR and p-p70 ribosomal protein S6 kinase. Furthermore, curcumin inhibited tumor angiogenesis in vivo. In conclusion, curcumin may be potent enough to be developed as a novel therapeutic agent for the treatment of MPM.