hispolon and Nasopharyngeal-Neoplasms

Hispolon has been reported to possess antioxidant, antiinflammatory, and antitumor activities. However, the effect of hispolon on the metastasis of nasopharyngeal carcinoma (NPC) remains unclear. In this study, we investigated how the antimetastatic activity and relevant signaling pathways of hispolon affected three NPC cell lines. The results revealed that hispolon significantly reduced the migration and invasion of three NPC cells in a dose-dependent manner from 0 to 50 µM. Hispolon also significantly inhibited the activity and expression of urokinase-plasminogen activator (uPA) as well as the phosphorylation of Akt. Moreover, blocking the Akt pathway also enhanced the antimetastatic ability of hispolon in the NPC cells. In conclusion, hispolon inhibited uPA expression and NPC cell metastasis by downregulating Akt signal pathways; therefore, hispolon exerts beneficial effects in chemoprevention. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 645-655, 2017.

Topics: Antineoplastic Agents; Carcinoma; Catechols; Cell Line, Tumor; Cell Movement; Cell Survival; Drug Screening Assays, Antitumor; Humans; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Neoplasm Invasiveness; Phosphorylation; Proteolysis; Proto-Oncogene Proteins c-akt; Signal Transduction; Urokinase-Type Plasminogen Activator

Hispolon, a phenol compound isolated from Phellinus linteus (PL), possesses anti-inflammatory, antiproliferative, and antioxidant effects. However, the effects of hispolon on human nasopharyngeal carcinomas have yet to be evaluated. Here, the molecular mechanism by which hispolon anticancer effects in human nasopharyngeal carcinomas cells was investigated. The results showed that hispolon significantly inhibited cell proliferation of HONE-1 and NP-039 cell lines. Furthermore, hispolon induced apoptosis through caspases-3, -8, and -9 activations and PARP cleavage in dose- and time-dependent manner in HONE-1 and NP-039 cells. Moreover, hispolon also showed that increase phosphorylation of ERK1/2, p38 MAPK and JNK1/2 in dose- and time-dependent manner by western blot analysis. However, hispolon-induced activation of the caspase-3, -8 and -9 significantly abolished by inhibition of p38 MAPK and JNK1/2 specific inhibitors. In this study, we determine that the effects of hispolon on the apoptosis and related regulation mechanism in HONE-1 and NPC-039 cells takes place. Our findings revealed that hispolon may be a useful candidate as a chemotherapeutic agent for NPC therapy.

Topics: Apoptosis; Basidiomycota; Carcinoma; Caspases; Catechols; Cell Line, Tumor; Cell Proliferation; Humans; MAP Kinase Signaling System; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Phosphorylation